Skip to main content

Prognostic Factors in AML

  • Chapter
  • First Online:
Acute Myeloid Leukemia

Part of the book series: Hematologic Malignancies ((HEMATOLOGIC))

Abstract

Prognosis of acute myeloid leukemia (AML) patients depends on patient-related features, disease manifestations at the time of presentation, and intrinsic disease-related genetic features, such as cytogenetic abnormalities and driver mutations. Prognostic stratification also depends on the therapeutic strategy and on response to treatment, including measurable residual disease assessment. This chapter reviews the influence of prognostic factors measured at the diagnosis of AML, with an emphasis on disease-related factors. The role of measurable residual disease and how prognostic stratification affects treatment decisions are covered in other chapters.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abaza Y, Cortes J, Ravandi F et al (2018) Prognostic significance of hyperdiploidy in adult acute myeloid leukemia. Am J Hematol 93(11):E357–E360

    Article  PubMed  Google Scholar 

  • Abbas S, Lugthart S, Kavelaars FG et al (2010) Acquired mutations in the genes encoding IDH1 and IDH2 both are recurrent aberrations in acute myeloid leukemia: prevalence and prognostic value. Blood 116(12):2122–2126

    Article  CAS  PubMed  Google Scholar 

  • Abbas HA, Ravandi F, Loghavi S et al (2019) NPM1 mutant variant allele frequency correlates with leukemia burden but does not provide prognostic information in NPM1-mutated acute myeloid leukemia. Am J Hematol 94(6):E158–E160

    Article  PubMed  PubMed Central  Google Scholar 

  • Ahn J-S, Kim H-J, Kim Y-K et al (2016) DNMT3A R882 mutation with FLT3-ITD positivity is an extremely poor prognostic factor in patients with normal-karyotype acute myeloid leukemia after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 22(1):61–70

    Article  CAS  PubMed  Google Scholar 

  • Ahn J-S, Kim H-J, Kim Y-K et al (2018) Assessment of a new genomic classification system in acute myeloid leukemia with a normal karyotype. Oncotarget 9(4):4961–4968

    Article  PubMed  Google Scholar 

  • Allen C, Hills RK, Lamb K et al (2013) The importance of relative mutant level for evaluating impact on outcome of KIT, FLT3 and CBL mutations in core-binding factor acute myeloid leukemia. Leukemia 27(9):1891–1901

    Article  CAS  PubMed  Google Scholar 

  • Andor N, Graham TA, Jansen M et al (2016) Pan-cancer analysis of the extent and consequences of intratumor heterogeneity. Nat Med 22(1):105–113

    Article  CAS  PubMed  Google Scholar 

  • Angenendt L, Röllig C, Montesinos P et al (2019) Chromosomal abnormalities and prognosis in NPM1-mutated acute myeloid Leukemia: a pooled analysis of individual patient data from nine international cohorts. JCO. 37(29):2632–2642

    Article  CAS  Google Scholar 

  • Appelbaum FR, Gundacker H, Head DR et al (2006a) Age and acute myeloid leukemia. Blood 107(9):3481–3485

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Appelbaum FR, Kopecky KJ, Tallman MS et al (2006b) The clinical spectrum of adult acute myeloid leukaemia associated with core binding factor translocations. Br J Haematol 135(2):165–173

    Article  PubMed  Google Scholar 

  • Arber DA, Orazi A, Hasserjian R et al (2016) The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127(20):2391–2405

    Article  CAS  PubMed  Google Scholar 

  • Armand P, Kim HT, DeAngelo DJ et al (2007) Impact of cytogenetics on outcome of de novo and therapy-related AML and MDS after allogeneic transplantation. Biol Blood Marrow Transplant 13(6):655–664

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arreba-Tutusaus P, Mack T, Bullinger L et al (2016) Impact of FLT3-ITD location on sensitivity to TKI-therapy in vitro and in vivo. Leukemia 30(5):1220–1225

    Article  CAS  PubMed  Google Scholar 

  • Bacher U, Haferlach C, Kern W, Haferlach T, Schnittger S (2008) Prognostic relevance of FLT3-TKD mutations in AML: the combination matters—an analysis of 3082 patients. Blood 111(5):2527–2537

    Article  CAS  PubMed  Google Scholar 

  • Baldus CD, Thiede C, Soucek S et al (2006) BAALC expression and FLT3 internal tandem duplication mutations in acute myeloid leukemia patients with normal cytogenetics: prognostic implications. J Clin Oncol 24(5):790–797

    Article  CAS  PubMed  Google Scholar 

  • Balgobind BV, Raimondi SC, Harbott J et al (2009) Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study. Blood 114(12):2489–2496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Balgobind BV, Zwaan CM, Pieters R, Van den Heuvel-Eibrink MM (2011) The heterogeneity of pediatric MLL-rearranged acute myeloid leukemia. Leukemia 25(8):1239–1248

    Article  CAS  PubMed  Google Scholar 

  • Balsat M, Renneville A, Thomas X et al (2017) Postinduction minimal residual disease predicts outcome and benefit from allogeneic stem cell transplantation in acute myeloid leukemia with NPM1 mutation: a study by the Acute Leukemia French Association Group. J Clin Oncol 35(2):185–193

    Article  CAS  PubMed  Google Scholar 

  • Barjesteh van Waalwijk van Doorn-Khosrovani S, Erpelinck C, van Putten WLJ et al (2003) High EVI1 expression predicts poor survival in acute myeloid leukemia: a study of 319 de novo AML patients. Blood 101(3):837–845

    Article  PubMed  CAS  Google Scholar 

  • Beck D, Thoms JAI, Palu C et al (2018) A four-gene LincRNA expression signature predicts risk in multiple cohorts of acute myeloid leukemia patients. Leukemia 32(2):263–272

    Article  CAS  PubMed  Google Scholar 

  • Becker H, Marcucci G, Maharry K et al (2010) Favorable prognostic impact of NPM1 mutations in older patients with cytogenetically normal de novo acute myeloid leukemia and associated gene- and microRNA-expression signatures: a Cancer and Leukemia Group B study. J Clin Oncol 28(4):596–604

    Article  CAS  PubMed  Google Scholar 

  • Bergua JM, Montesinos P, Martinez-Cuadrón D et al (2016) A prognostic model for survival after salvage treatment with FLAG-Ida +/− gemtuzumab-ozogamicine in adult patients with refractory/relapsed acute myeloid leukaemia. Br J Haematol 174(5):700–710

    Article  CAS  PubMed  Google Scholar 

  • Bezerra MF, Lima AS, Piqué-Borràs M-R et al (2020) Co-occurrence of DNMT3A, NPM1, FLT3 mutations identifies a subset of acute myeloid leukemia with adverse prognosis. Blood 135(11):870–875

    Article  PubMed  Google Scholar 

  • Bhatnagar B, Blachly JS, Kohlschmidt J et al (2016) Clinical features and gene- and microRNA-expression patterns in adult acute leukemia patients with t(11;19)(q23;p13.1) and t(11;19)(q23;p13.3). Leukemia 30(7):1586–1589

    Article  CAS  PubMed  Google Scholar 

  • Bhatt VR (2019) Personalizing therapy for older adults with acute myeloid leukemia: role of geriatric assessment and genetic profiling. Cancer Treat Rev 75:52–61

    Article  PubMed  Google Scholar 

  • Bill M, Nicolet D, Kohlschmidt J et al (2020) Mutations associated with a 17-gene leukemia stem cell score and the score’s prognostic relevance in the context of the European LeukemiaNet classification of acute myeloid leukemia. Haematologica 105(3):721–729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blau O, Berenstein R, Sindram A, Blau IW (2013) Molecular analysis of different FLT3-ITD mutations in acute myeloid leukemia. Leuk Lymphoma 54(1):145–152

    Article  CAS  PubMed  Google Scholar 

  • Bloomfield CD, Archer KJ, Mrózek K et al (2002) 11q23 balanced chromosome aberrations in treatment-related myelodysplastic syndromes and acute leukemia: report from an international workshop. Genes Chromosomes Cancer 33(4):362–378

    Article  PubMed  Google Scholar 

  • Bochtler T, Stölzel F, Heilig CE et al (2013) Clonal heterogeneity as detected by metaphase karyotyping is an indicator of poor prognosis in acute myeloid leukemia. J Clin Oncol 31(31):3898–3905

    Article  PubMed  Google Scholar 

  • Bochtler T, Granzow M, Stölzel F et al (2017) Marker chromosomes can arise from chromothripsis and predict adverse prognosis in acute myeloid leukemia. Blood 129(10):1333–1342

    Article  CAS  PubMed  Google Scholar 

  • Boddu P, Kantarjian H, Borthakur G et al (2017) Co-occurrence of FLT3-TKD and NPM1 mutations defines a highly favorable prognostic AML group. Blood Adv 1(19):1546–1550

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boddu P, Gurguis C, Sanford D et al (2018) Response kinetics and factors predicting survival in core-binding factor leukemia. Leukemia 32(12):2698–2701

    Article  CAS  PubMed  Google Scholar 

  • Boddu PC, Kadia TM, Garcia-Manero G et al (2019) Validation of the 2017 European LeukemiaNet classification for acute myeloid leukemia with NPM1 and FLT3-internal tandem duplication genotypes. Cancer 125(7):1091–1100

    Article  CAS  PubMed  Google Scholar 

  • Boissel N, Renneville A, Biggio V et al (2005) Prevalence, clinical profile, and prognosis of NPM mutations in AML with normal karyotype. Blood 106(10):3618–3620

    Article  CAS  PubMed  Google Scholar 

  • Boissel N, Leroy H, Brethon B et al (2006) Incidence and prognostic impact of c-kit, FLT3, and Ras gene mutations in core binding factor acute myeloid leukemia (CBF-AML). Leukemia 20(6):965–970

    Article  CAS  PubMed  Google Scholar 

  • Boissel N, Nibourel O, Renneville A et al (2010) Prognostic impact of isocitrate dehydrogenase enzyme isoforms 1 and 2 mutations in acute myeloid leukemia: a study by the Acute Leukemia French Association Group. J Clin Oncol 28(23):3717–3723

    Article  CAS  PubMed  Google Scholar 

  • Boissel N, Nibourel O, Renneville A et al (2011) Differential prognosis impact of IDH2 mutations in cytogenetically normal acute myeloid leukemia. Blood 117(13):3696–3697

    Article  CAS  PubMed  Google Scholar 

  • Bolouri H, Farrar JE, Triche T et al (2018) The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions. Nat Med 24(1):103–112

    Article  CAS  PubMed  Google Scholar 

  • Bonanad S, De la Rubia J, Gironella M et al (2015) Development and psychometric validation of a brief comprehensive health status assessment scale in older patients with hematological malignancies: the GAH scale. J Geriatr Oncol 6(5):353–361

    Article  CAS  PubMed  Google Scholar 

  • Bowen D, Groves MJ, Burnett AK et al (2009) TP53 gene mutation is frequent in patients with acute myeloid leukemia and complex karyotype, and is associated with very poor prognosis. Leukemia 23(1):203–206

    Article  CAS  PubMed  Google Scholar 

  • Bower H, Andersson TM-L, Björkholm M et al (2016) Continued improvement in survival of acute myeloid leukemia patients: an application of the loss in expectation of life. Blood Cancer J 6(2):e390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Braun T, Cereja S, Chevret S et al (2015) Evolving characteristics and outcome of secondary acute promyelocytic leukemia (APL): a prospective analysis by the French-Belgian-Swiss APL Group. Cancer 121(14):2393–2399

    Article  CAS  PubMed  Google Scholar 

  • Breems DA, Van Putten WLJ, Huijgens PC et al (2005) Prognostic index for adult patients with acute myeloid leukemia in first relapse. J Clin Oncol 23(9):1969–1978

    Article  PubMed  Google Scholar 

  • Breems DA, Van Putten WLJ, De Greef GE et al (2008) Monosomal karyotype in acute myeloid leukemia: a better indicator of poor prognosis than a complex karyotype. J Clin Oncol 26(29):4791–4797

    Article  PubMed  Google Scholar 

  • Büchner T, Berdel WE, Haferlach C et al (2009) Age-related risk profile and chemotherapy dose response in acute myeloid leukemia: a study by the German Acute Myeloid Leukemia Cooperative Group. J Clin Oncol 27(1):61–69

    Article  PubMed  CAS  Google Scholar 

  • Bullinger L, Döhner K, Bair E et al (2004) Use of gene-expression profiling to identify prognostic subclasses in adult acute myeloid leukemia. N Engl J Med 350(16):1605–1616

    Article  CAS  PubMed  Google Scholar 

  • Bullinger L, Ehrich M, Döhner K et al (2010) Quantitative DNA methylation predicts survival in adult acute myeloid leukemia. Blood 115(3):636–642

    Article  CAS  PubMed  Google Scholar 

  • Bullinger L, Döhner K, Döhner H (2017) Genomics of acute myeloid leukemia diagnosis and pathways. J Clin Oncol 35(9):934–946

    Article  CAS  PubMed  Google Scholar 

  • Bullinger L, Valk P, Versluis J et al (2019) Harmony alliance: European public-private data collection leads the way—first results of the “proof-of-principle” study in acute myeloid leukemia: PS1003. HemaSphere 3:451

    Article  Google Scholar 

  • Burnett AK, Russell NH, Hills RK et al (2013) Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the Medical Research Council AML15 trial. J Clin Oncol 31(27):3360–3368

    Article  CAS  PubMed  Google Scholar 

  • Byrd JC, Weiss RB, Arthur DC et al (1997) Extramedullary leukemia adversely affects hematologic complete remission rate and overall survival in patients with t(8;21)(q22;q22): results from Cancer and Leukemia Group B 8461. J Clin Oncol 15(2):466–475

    Article  CAS  PubMed  Google Scholar 

  • Byrd JC, Mrózek K, Dodge RK et al (2002) Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461) presented in part at the 43rd annual meeting of the American Society of Hematology, Orlando, FL, December 10, 2001, and published in abstract form.59. Blood 100(13):4325–4336

    Article  CAS  PubMed  Google Scholar 

  • Cairo MS, Bishop M (2004) Tumour lysis syndrome: new therapeutic strategies and classification. Br J Haematol 127(1):3–11

    Article  PubMed  Google Scholar 

  • Cairoli R, Beghini A, Grillo G et al (2006) Prognostic impact of c-KIT mutations in core binding factor leukemias: an Italian retrospective study. Blood 107(9):3463–3468

    Article  CAS  PubMed  Google Scholar 

  • Canaani J, Labopin M, Socié G et al (2017) Long term impact of hyperleukocytosis in newly diagnosed acute myeloid leukemia patients undergoing allogeneic stem cell transplantation: an analysis from the acute leukemia working party of the EBMT: Canaani et al. Am J Hematol 92(7):653–659

    Article  CAS  PubMed  Google Scholar 

  • Canaani J, Labopin M, Itälä-Remes M et al (2019) Prognostic significance of recurring chromosomal abnormalities in transplanted patients with acute myeloid leukemia. Leukemia 33(8):1944–1952

    Article  CAS  PubMed  Google Scholar 

  • Cannas G, Pautas C, Raffoux E et al (2012) Infectious complications in adult acute myeloid leukemia: analysis of the Acute Leukemia French Association-9802 prospective multicenter clinical trial. Leuk Lymphoma 53(6):1068–1076

    Article  CAS  PubMed  Google Scholar 

  • Care RS, Valk PJM, Goodeve AC et al (2003) Incidence and prognosis of c-KIT and FLT3 mutations in core binding factor (CBF) acute myeloid leukaemias. Br J Haematol 121(5):775–777

    Article  CAS  PubMed  Google Scholar 

  • Carter BZ, Qiu Y, Huang X et al (2012) Survivin is highly expressed in CD34+38− leukemic stem/progenitor cells and predicts poor clinical outcomes in AML. Blood 120(1):173–180

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cerrano M, Itzykson R (2019) New treatment options for acute myeloid leukemia in 2019. Curr Oncol Rep 21(2):16

    Article  PubMed  Google Scholar 

  • Cerrano M, Duchmann M, Kim R et al (2021) Clonal dominance is an adverse prognostic factor in acute myeloid leukemia treated with intensive chemotherapy. Leukemia 35(3):712–723

    Article  CAS  PubMed  Google Scholar 

  • Chang H, Brandwein J, Yi Q-L et al (2004) Extramedullary infiltrates of AML are associated with CD56 expression, 11q23 abnormalities and inferior clinical outcome. Leuk Res 28(10):1007–1011

    Article  CAS  PubMed  Google Scholar 

  • Chen Y, Kantarjian H, Pierce S et al (2013) Prognostic significance of 11q23 aberrations in adult acute myeloid leukemia and the role of allogeneic stem cell transplantation. Leukemia 27(4):836–842

    Article  CAS  PubMed  Google Scholar 

  • Chen W, Xie H, Wang H et al (2016) Prognostic significance of KIT mutations in core-binding factor acute myeloid leukemia: a systematic review and meta-analysis. PLoS One 11(1):e0146614

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chen F, Sun J, Yin C et al (2019) Impact of FLT3-ITD allele ratio and ITD length on therapeutic outcome in cytogenetically normal AML patients without NPM1 mutation. Bone Marrow Transplant 55(4):740–748

    Article  PubMed  CAS  Google Scholar 

  • Cheng C-L, Li C-C, Hou H-A et al (2015) Risk factors and clinical outcomes of acute myeloid leukaemia with central nervous system involvement in adults. BMC Cancer 15(1):344

    Article  PubMed  PubMed Central  Google Scholar 

  • Cher CY, Leung GMK, Au CH et al (2016) Next-generation sequencing with a myeloid gene panel in core-binding factor AML showed KIT activation loop and TET2 mutations predictive of outcome. Blood Cancer J 6(7):e442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chevallier P, Labopin M, Turlure P et al (2011) A new leukemia prognostic scoring system for refractory/relapsed adult acute myelogeneous leukaemia patients: a GOELAMS study. Leukemia 25(6):939–944

    Article  CAS  PubMed  Google Scholar 

  • Chilton L, Hills RK, Harrison CJ et al (2014) Hyperdiploidy with 49-65 chromosomes represents a heterogeneous cytogenetic subgroup of acute myeloid leukemia with differential outcome. Leukemia 28(2):321–328

    Article  CAS  PubMed  Google Scholar 

  • Chisini M, Stefanizzi C, Ceglie T et al (2017) Independent prognostic impact of CD15 on complete remission achievement in patients with acute myeloid leukemia. Hematol Oncol 35(4):804–809

    Article  CAS  PubMed  Google Scholar 

  • Chou W-C, Huang H-H, Hou H-A et al (2010) Distinct clinical and biological features of de novo acute myeloid leukemia with additional sex comb-like 1 (ASXL1) mutations. Blood 116(20):4086–4094

    Article  CAS  PubMed  Google Scholar 

  • Chou W-C, Chou S-C, Liu C-Y et al (2011a) TET2 mutation is an unfavorable prognostic factor in acute myeloid leukemia patients with intermediate-risk cytogenetics. Blood 118(14):3803–3810

    Article  CAS  PubMed  Google Scholar 

  • Chou W-C, Lei W-C, Ko B-S et al (2011b) The prognostic impact and stability of isocitrate dehydrogenase 2 mutation in adult patients with acute myeloid leukemia. Leukemia 25(2):246–253

    Article  CAS  PubMed  Google Scholar 

  • Christen F, Hoyer K, Yoshida K et al (2019) Genomic landscape and clonal evolution of acute myeloid leukemia with t(8;21): an international study on 331 patients. Blood 133(10):1140–1151

    Article  CAS  PubMed  Google Scholar 

  • Christiansen DH, Andersen MK, Pedersen-Bjergaard J (2001) Mutations with loss of heterozygosity of p53 are common in therapy-related myelodysplasia and acute myeloid leukemia after exposure to alkylating agents and significantly associated with deletion or loss of 5q, a complex karyotype, and a poor prognosis. J Clin Oncol 19(5):1405–1413

    Article  CAS  PubMed  Google Scholar 

  • Christiansen DH, Andersen MK, Pedersen-Bjergaard J (2016) Mutations with loss of heterozygosity of p53 are common in therapy-related myelodysplasia and acute myeloid leukemia after exposure to alkylating agents and significantly associated with deletion or loss of 5q, a complex karyotype, and a poor prognosis. J Clin Oncol 19(5):1405–1413

    Article  Google Scholar 

  • Ciurea SO, Chilkulwar A, Saliba RM et al (2018) Prognostic factors influencing survival after allogeneic transplantation for AML/MDS patients with TP53 mutations. Blood 131(26):2989–2992

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cornelissen JJ, Blaise D (2016) Hematopoietic stem cell transplantation for patients with AML in first complete remission. Blood 127(1):62–70

    Article  CAS  PubMed  Google Scholar 

  • Cornelissen JJ, Gratwohl A, Schlenk RF et al (2012) The European LeukemiaNet AML working party consensus statement on allogeneic HCT for patients with AML in remission: an integrated-risk adapted approach. Nat Rev Clin Oncol 9(10):579–590

    Google Scholar 

  • Costa AFO, Menezes DL, Pinheiro LHS et al (2017) Role of new Immunophenotypic markers on prognostic and overall survival of acute myeloid leukemia: a systematic review and meta-analysis. Sci Rep 7(1):4138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Creutzig U, Zimmermann M, Reinhardt D et al (2016) Changes in cytogenetics and molecular genetics in acute myeloid leukemia from childhood to adult age groups. Cancer 122(24):3821–3830

    Article  CAS  PubMed  Google Scholar 

  • Damm F, Heuser M, Morgan M et al (2011) Integrative prognostic risk score in acute myeloid leukemia with normal karyotype. Blood 117(17):4561–4568

    Article  CAS  PubMed  Google Scholar 

  • Daver N, Liu Dumlao T, Ravandi F et al (2013) Effect of NPM1 and FLT3 mutations on the outcomes of elderly patients with acute myeloid leukemia receiving standard chemotherapy. Clin Lymphoma Myeloma Leuk 13(4):435–440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Daver N, Schlenk RF, Russell NH, Levis MJ (2019) Targeting FLT3 mutations in AML: review of current knowledge and evidence. Leukemia 33(2):299–312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • de Jonge HJM, Valk PJM, de Bont ESJM et al (2011) Prognostic impact of white blood cell count in intermediate risk acute myeloid leukemia: relevance of mutated NPM1 and FLT3-ITD. Haematologica 96(9):1310–1317

    Article  PubMed  PubMed Central  Google Scholar 

  • de Rooij JDE, Branstetter C, Ma J et al (2017) Pediatric non–Down syndrome acute megakaryoblastic leukemia is characterized by distinct genomic subsets with varying outcomes. Nat Genet 49(3):451–456

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • De Stefano V, Sorà F, Rossi E et al (2005) The risk of thrombosis in patients with acute leukemia: occurrence of thrombosis at diagnosis and during treatment. J Thromb Haemost 3(9):1985–1992

    Article  PubMed  Google Scholar 

  • Del Poeta G, Venditti A, Del Principe MI et al (2003) Amount of spontaneous apoptosis detected by Bax/Bcl-2 ratio predicts outcome in acute myeloid leukemia (AML). Blood 101(6):2125–2131

    Article  PubMed  CAS  Google Scholar 

  • Del Principe MI, Buccisano F, Soddu S et al (2018) Involvement of central nervous system in adult patients with acute myeloid leukemia: incidence and impact on outcome. Semin Hematol 55(4):209–214

    Article  PubMed  Google Scholar 

  • Della Porta MG, Gallì A, Bacigalupo A et al (2016) Clinical effects of driver somatic mutations on the outcomes of patients with myelodysplastic syndromes treated with allogeneic hematopoietic stem-cell transplantation. J Clin Oncol 34(30):3627–3637

    Article  PubMed  PubMed Central  Google Scholar 

  • Deneberg S, Grövdal M, Karimi M et al (2010) Gene-specific and global methylation patterns predict outcome in patients with acute myeloid leukemia. Leukemia 24(5):932–941

    Article  CAS  PubMed  Google Scholar 

  • Deneberg S, Guardiola P, Lennartsson A et al (2011) Prognostic DNA methylation patterns in cytogenetically normal acute myeloid leukemia are predefined by stem cell chromatin marks. Blood 118(20):5573–5582

    Article  CAS  PubMed  Google Scholar 

  • Devillier R, Mansat-De Mas V, Gelsi-Boyer V et al (2015a) Role of ASXL1 and TP53 mutations in the molecular classification and prognosis of acute myeloid leukemias with myelodysplasia-related changes. Oncotarget 6(10):8388–8396

    Article  PubMed  PubMed Central  Google Scholar 

  • Devillier R, Gelsi-Boyer V, Murati A et al (2015b) Prognostic significance of myelodysplasia-related changes according to the WHO classification among ELN-intermediate-risk AML patients. Am J Hematol 90(1):E22–E24

    Article  PubMed  Google Scholar 

  • Díaz-Beyá M, Brunet S, Nomdedéu J et al (2014) MicroRNA expression at diagnosis adds relevant prognostic information to molecular categorization in patients with intermediate-risk cytogenetic acute myeloid leukemia. Leukemia 28(4):804–812

    Article  PubMed  CAS  Google Scholar 

  • Díaz-Beyá M, Labopin M, Maertens J et al (2020) Allogeneic stem cell transplantation in AML with t(6;9)(p23;q34);DEK-NUP214 shows a favourable outcome when performed in first complete remission. Br J Haematol 189(5):920–925

    Article  PubMed  CAS  Google Scholar 

  • Dicker F, Haferlach C, Sundermann J et al (2010) Mutation analysis for RUNX1, MLL-PTD, FLT3-ITD, NPM1 and NRAS in 269 patients with MDS or secondary AML. Leukemia 24(8):1528–1532

    Article  CAS  PubMed  Google Scholar 

  • DiNardo CD, Luskin MR, Carroll M et al (2017) Validation of a clinical assay of multi-locus DNA methylation for prognosis of newly diagnosed AML. Am J Hematol 92(2):E14–E15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • DiNardo CD, Pratz K, Pullarkat V et al (2019) Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood 133(1):7–17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Döhner K, Tobis K, Ulrich R et al (2002) Prognostic significance of partial tandem duplications of the MLL gene in adult patients 16 to 60 years old with acute myeloid leukemia and normal cytogenetics: a study of the Acute Myeloid Leukemia Study Group Ulm. J Clin Oncol 20(15):3254–3261

    Article  PubMed  CAS  Google Scholar 

  • Döhner K, Schlenk RF, Habdank M et al (2005) Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics: interaction with other gene mutations. Blood 106(12):3740–3746

    Article  PubMed  CAS  Google Scholar 

  • Döhner H, Estey EH, Amadori S et al (2010) Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 115(3):453–474

    Article  PubMed  CAS  Google Scholar 

  • Döhner H, Estey E, Grimwade D et al (2017) Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 129(4):424–447

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Döhner K, Thiede C, Jahn N et al (2020) Impact of NPM1/FLT3-ITD genotypes defined by the 2017 European LeukemiaNet in patients with acute myeloid leukemia. Blood 135(5):371–380

    Article  PubMed  PubMed Central  Google Scholar 

  • Driessen EMC, van Roon EHJ, Spijkers-Hagelstein JAP et al (2013) Frequencies and prognostic impact of RAS mutations in MLL-rearranged acute lymphoblastic leukemia in infants. Haematologica 98(6):937–944

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dufour A, Schneider F, Metzeler KH et al (2010) Acute myeloid leukemia with biallelic CEBPA gene mutations and normal karyotype represents a distinct genetic entity associated with a favorable clinical outcome. J Clin Oncol 28(4):570–577

    Article  CAS  PubMed  Google Scholar 

  • Dunlap JB, Leonard J, Rosenberg M et al (2019) The combination of NPM1, DNMT3A, and IDH1/2 mutations leads to inferior overall survival in AML. Am J Hematol 94(8):913–920

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Duployez N, Marceau-Renaut A, Boissel N et al (2016) Comprehensive mutational profiling of core binding factor acute myeloid leukemia. Blood 127(20):2451–2459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Duployez N, Boudry-Labis E, Roumier C et al (2018) SNP-array lesions in core binding factor acute myeloid leukemia. Oncotarget 9(5):6478–6489

    Article  PubMed  PubMed Central  Google Scholar 

  • Duployez N, Marceau-Renaut A, Villenet C et al (2019) The stem cell-associated gene expression signature allows risk stratification in pediatric acute myeloid leukemia. Leukemia 33(2):348–357

    Article  CAS  PubMed  Google Scholar 

  • Eisfeld A-K, Mrózek K, Kohlschmidt J et al (2017) The mutational oncoprint of recurrent cytogenetic abnormalities in adult patients with de novo acute myeloid leukemia. Leukemia 31(10):2211–2218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eisfeld A-K, Kohlschmidt J, Mrózek K et al (2018) Mutation patterns identify adult patients with de novo acute myeloid leukemia aged 60 years or older who respond favorably to standard chemotherapy: an analysis of alliance studies. Leukemia 32(6):1338–1348

    Article  PubMed  PubMed Central  Google Scholar 

  • El-Sharkawi D, Sproul D, Allen CG et al (2018) Variable outcome and methylation status according to CEBPA mutant type in double-mutated acute myeloid leukemia patients and the possible implications for treatment. Haematologica 103(1):91–100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eppert K, Takenaka K, Lechman ER et al (2011) Stem cell gene expression programs influence clinical outcome in human leukemia. Nat Med 17(9):1086–1093

    Article  CAS  PubMed  Google Scholar 

  • Esposito MT (2019) The impact of PI3-kinase/RAS pathway cooperating mutations in the evolution of KMT2A-rearranged leukemia. Hemasphere 3(3):e195

    Article  PubMed  PubMed Central  Google Scholar 

  • Estey E, Gale RP (2017) How good are we at predicting the fate of someone with acute myeloid leukaemia? Leukemia 31(6):1255–1258

    Article  CAS  PubMed  Google Scholar 

  • Faber ZJ, Chen X, Gedman AL et al (2016) The genomic landscape of core-binding factor acute myeloid leukemias. Nat Genet 48(12):1551–1556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Falini B, Mecucci C, Tiacci E et al (2005) Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med 352(3):254–266

    Article  CAS  PubMed  Google Scholar 

  • Farag SS, Archer KJ, Mrózek K et al (2006) Pretreatment cytogenetics add to other prognostic factors predicting complete remission and long-term outcome in patients 60 years of age or older with acute myeloid leukemia: results from Cancer and Leukemia Group B 8461. Blood 108(1):63–73

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fasan A, Eder C, Haferlach C et al (2013) GATA2 mutations are frequent in intermediate-risk karyotype AML with biallelic CEBPA mutations and are associated with favorable prognosis. Leukemia 27(2):482–485

    Article  CAS  PubMed  Google Scholar 

  • Fasan A, Haferlach C, Alpermann T et al (2014) The role of different genetic subtypes of CEBPA mutated AML. Leukemia 28(4):794–803

    Article  CAS  PubMed  Google Scholar 

  • Fenwarth L, Itzykson R, De Botton S et al (2019) Integrating ELN criteria and a “knowledge bank” approach to guide allogeneic stem cell transplantation (SCT) indication in younger adults with acute myeloid leukemia (AML): an Acute Leukemia French Association Study. Blood 134(Suppl_1):1423

    Article  Google Scholar 

  • Figueroa ME, Lugthart S, Li Y et al (2010) DNA methylation signatures identify biologically distinct subtypes in acute myeloid leukemia. Cancer Cell 17(1):13–27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fischer M, Schnetzke U, Spies-Weisshart B et al (2017) Impact of FLT3-ITD diversity on response to induction chemotherapy in patients with acute myeloid leukemia. Haematologica 102(4):e129–e131

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fontana MC, Marconi G, Feenstra JDM et al (2018) Chromothripsis in acute myeloid leukemia: biological features and impact on survival. Leukemia 32(7):1609–1620

    Article  PubMed  PubMed Central  Google Scholar 

  • Fröhling S, Schlenk RF, Breitruck J et al (2002) Prognostic significance of activating FLT3 mutations in younger adults (16 to 60 years) with acute myeloid leukemia and normal cytogenetics: a study of the AML Study Group Ulm. Blood 100(13):4372–4380

    Article  PubMed  CAS  Google Scholar 

  • Fröhling S, Schlenk RF, Stolze I et al (2004) CEBPA mutations in younger adults with acute myeloid leukemia and normal cytogenetics: prognostic relevance and analysis of cooperating mutations. J Clin Oncol 22(4):624–633

    Article  PubMed  CAS  Google Scholar 

  • Fröhling S, Schlenk RF, Kayser S et al (2006) Cytogenetics and age are major determinants of outcome in intensively treated acute myeloid leukemia patients older than 60 years: results from AMLSG trial AML HD98-B. Blood 108(10):3280–3288

    Article  PubMed  CAS  Google Scholar 

  • Fujiwara S, Muroi K, Yamamoto C et al (2017) CD25 as an adverse prognostic factor in elderly patients with acute myeloid leukemia. Hematology 22(6):347–353

    Article  CAS  PubMed  Google Scholar 

  • Gaidzik VI, Schlenk RF, Moschny S et al (2009) Prognostic impact of WT1 mutations in cytogenetically normal acute myeloid leukemia: a study of the German-Austrian AML Study Group. Blood 113(19):4505–4511

    Article  CAS  PubMed  Google Scholar 

  • Gaidzik VI, Bullinger L, Schlenk RF et al (2011) RUNX1 mutations in acute myeloid leukemia: results from a comprehensive genetic and clinical analysis from the AML Study Group. J Clin Oncol 29(10):1364–1372

    Article  PubMed  Google Scholar 

  • Gaidzik VI, Paschka P, Späth D et al (2012) TET2 mutations in acute myeloid leukemia (AML): results from a comprehensive genetic and clinical analysis of the AML Study Group. J Clin Oncol 30(12):1350–1357

    Article  CAS  PubMed  Google Scholar 

  • Gaidzik VI, Schlenk RF, Paschka P et al (2013) Clinical impact of DNMT3A mutations in younger adult patients with acute myeloid leukemia: results of the AML Study Group (AMLSG). Blood 121(23):4769–4777

    Article  CAS  PubMed  Google Scholar 

  • Gaidzik VI, Teleanu V, Papaemmanuil E et al (2016) RUNX1 mutations in acute myeloid leukemia are associated with distinct clinico-pathologic and genetic features. Leukemia 30(11):2160–2168

    Article  CAS  PubMed  Google Scholar 

  • Gale RE, Green C, Allen C et al (2008) The impact of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia. Blood 111(5):2776–2784

    Article  CAS  PubMed  Google Scholar 

  • Ganzel C, Becker J, Mintz PD, Lazarus HM, Rowe JM (2012) Hyperleukocytosis, leukostasis and leukapheresis: practice management. Blood Rev 26(3):117–122

    Article  PubMed  Google Scholar 

  • Ganzel C, Manola J, Douer D et al (2016) Extramedullary disease in adult acute myeloid leukemia is common but lacks independent significance: analysis of patients in ECOG-ACRIN Cancer research group trials, 1980-2008. J Clin Oncol 34(29):3544–3553

    Article  PubMed  PubMed Central  Google Scholar 

  • Gardin C, Pautas C, Fournier E et al (2020) Added prognostic value of secondary AML-like gene mutations in ELN intermediate-risk older AML: ALFA-1200 study results. Blood Adv 4(9):1942–1949

    Article  PubMed  PubMed Central  Google Scholar 

  • Gentles AJ, Plevritis SK, Majeti R, Alizadeh AA (2010) Association of a leukemic stem cell gene expression signature with clinical outcomes in acute myeloid leukemia. JAMA 304(24):2706–2715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gerstung M, Papaemmanuil E, Martincorena I et al (2017) Precision oncology for acute myeloid leukemia using a knowledge bank approach. Nat Genet 49(3):332–340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Giammarco S, Chiusolo P, Piccirillo N et al (2017) Hyperleukocytosis and leukostasis: management of a medical emergency. Expert Rev Hematol 10(2):147–154

    Article  CAS  PubMed  Google Scholar 

  • Granfeldt Østgård LS, Medeiros BC, Sengeløv H et al (2015) Epidemiology and clinical significance of secondary and therapy-related acute myeloid Leukemia: a National Population-Based Cohort Study. JCO 33(31):3641–3649

    Article  Google Scholar 

  • Green CL, Koo KK, Hills RK et al (2010) Prognostic significance of CEBPA mutations in a large cohort of younger adult patients with acute myeloid leukemia: impact of double CEBPA mutations and the interaction with FLT3 and NPM1 mutations. J Clin Oncol 28(16):2739–2747

    Article  CAS  PubMed  Google Scholar 

  • Green CL, Evans CM, Zhao L et al (2011) The prognostic significance of IDH2 mutations in AML depends on the location of the mutation. Blood 118(2):409–412

    Article  CAS  PubMed  Google Scholar 

  • Greenberg PL, Tuechler H, Schanz J et al (2012) Revised international prognostic scoring system for myelodysplastic syndromes. Blood 120(12):2454–2465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Greif PA, Konstandin NP, Metzeler KH et al (2012) RUNX1 mutations in cytogenetically normal acute myeloid leukemia are associated with a poor prognosis and up-regulation of lymphoid genes. Haematologica 97(12):1909–1915

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Greif PA, Hartmann L, Vosberg S et al (2018) Evolution of cytogenetically normal acute myeloid Leukemia during therapy and relapse: an exome sequencing study of 50 patients. Clin Cancer Res 24(7):1716–1726

    Article  CAS  PubMed  Google Scholar 

  • Grimwade D, Mrózek K (2011) Diagnostic and prognostic value of cytogenetics in acute myeloid Leukemia. Hematol Oncol Clin North Am 25(6):1135–1161

    Article  PubMed  Google Scholar 

  • Grimwade D, Walker H, Oliver F et al (1998) The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children’s Leukaemia Working Parties. Blood 92(7):2322–2333

    Article  CAS  PubMed  Google Scholar 

  • Grimwade D, Walker H, Harrison G et al (2001) The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial. Blood 98(5):1312–1320

    Article  CAS  PubMed  Google Scholar 

  • Grimwade D, Hills RK, Moorman AV et al (2010) Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood 116(3):354–365

    Article  CAS  PubMed  Google Scholar 

  • Grimwade D, Ivey A, Huntly BJP (2016) Molecular landscape of acute myeloid leukemia in younger adults and its clinical relevance. Blood 127(1):29–41

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gröschel S, Lugthart S, Schlenk RF et al (2010) High EVI1 expression predicts outcome in younger adult patients with acute myeloid leukemia and is associated with distinct cytogenetic abnormalities. J Clin Oncol 28(12):2101–2107

    Article  PubMed  CAS  Google Scholar 

  • Gröschel S, Schlenk RF, Engelmann J et al (2013) Deregulated expression of EVI1 defines a poor prognostic subset of MLL-rearranged acute myeloid leukemias: a study of the German-Austrian Acute Myeloid Leukemia Study Group and the Dutch-Belgian-Swiss HOVON/SAKK Cooperative Group. J Clin Oncol 31(1):95–103

    Article  PubMed  Google Scholar 

  • Grossmann V, Schnittger S, Kohlmann A et al (2012) A novel hierarchical prognostic model of AML solely based on molecular mutations. Blood 120(15):2963–2972

    Article  CAS  PubMed  Google Scholar 

  • Grossmann V, Haferlach C, Nadarajah N et al (2013a) CEBPA double-mutated acute myeloid leukaemia harbours concomitant molecular mutations in 76·8% of cases with TET2 and GATA2 alterations impacting prognosis. Br J Haematol 161(5):649–658

    Article  CAS  PubMed  Google Scholar 

  • Grossmann V, Schnittger S, Poetzinger F et al (2013b) High incidence of RAS signalling pathway mutations in MLL-rearranged acute myeloid leukemia. Leukemia 27(9):1933–1936

    Article  CAS  PubMed  Google Scholar 

  • Haferlach C, Dicker F, Herholz H et al (2008) Mutations of the TP53 gene in acute myeloid leukemia are strongly associated with a complex aberrant karyotype. Leukemia 22(8):1539–1541

    Article  CAS  PubMed  Google Scholar 

  • Haferlach C, Mecucci C, Schnittger S et al (2009) AML with mutated NPM1 carrying a normal or aberrant karyotype show overlapping biologic, pathologic, immunophenotypic, and prognostic features. Blood 114(14):3024–3032

    Article  CAS  PubMed  Google Scholar 

  • Haferlach C, Alpermann T, Schnittger S et al (2012) Prognostic value of monosomal karyotype in comparison to complex aberrant karyotype in acute myeloid leukemia: a study on 824 cases with aberrant karyotype. Blood 119(9):2122–2125

    Article  CAS  PubMed  Google Scholar 

  • Harada Y, Nagata Y, Kihara R et al (2018) Prognostic analysis according to the 2017 ELN risk stratification by genetics in adult acute myeloid leukemia patients treated in the Japan Adult Leukemia Study Group (JALSG) AML201 study. Leuk Res 66:20–27

    Article  PubMed  Google Scholar 

  • Harrison CJ, Hills RK, Moorman AV et al (2010) Cytogenetics of childhood acute myeloid leukemia: United Kingdom Medical Research Council treatment trials AML 10 and 12. J Clin Oncol 28(16):2674–2681

    Article  PubMed  Google Scholar 

  • Hefazi M, Siddiqui M, Patnaik M et al (2015) Prognostic impact of combined NPM1+/FLT3− genotype in patients with acute myeloid leukemia with intermediate risk cytogenetics stratified by age and treatment modalities. Leuk Res 39(11):1207–1213

    Article  CAS  Google Scholar 

  • Heiblig M, Labussière-Wallet H, Nicolini FE et al (2019) Prognostic value of genetic alterations in elderly patients with acute myeloid leukemia: a single institution experience. Cancers (Basel) 11(4):570

    Article  CAS  Google Scholar 

  • Herold T, Jurinovic V, Batcha AMN et al (2018) A 29-gene and cytogenetic score for the prediction of resistance to induction treatment in acute myeloid leukemia. Haematologica 103(3):456–465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Herold T, Rothenberg-Thurley M, Grunwald VV et al (2020) Validation and refinement of the revised 2017 European LeukemiaNet genetic risk stratification of acute myeloid leukemia. Leukemia 34:3161–3172

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Heuser M (2016) Therapy-related myeloid neoplasms: does knowing the origin help to guide treatment? Hematology Am Soc Hematol Educ Program 2016(1):24–32

    Article  PubMed  PubMed Central  Google Scholar 

  • Hinai AA, Valk PJM (2016) Review: aberrant EVI1 expression in acute myeloid leukaemia. Br J Haematol 172(6):870–878

    Article  CAS  PubMed  Google Scholar 

  • Hinai ASAA, Pratcorona M, Grob T et al (2019) The landscape of KMT2A-PTD AML: concurrent mutations, gene expression signatures, and clinical outcome. Hemasphere 3(2):e181

    Article  PubMed  PubMed Central  Google Scholar 

  • Ho PA, Kopecky KJ, Alonzo TA et al (2011) Prognostic implications of the IDH1 synonymous SNP rs11554137 in pediatric and adult AML: a report from the Children’s Oncology Group and SWOG. Blood 118(17):4561–4566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ho AD, Schetelig J, Bochtler T et al (2016) Allogeneic stem cell transplantation improves survival in patients with acute myeloid Leukemia characterized by a high allelic ratio of mutant FLT3-ITD. Biol Blood Marrow Transplant 22(3):462–469

    Article  CAS  PubMed  Google Scholar 

  • Hollink IHIM, Zwaan CM, Zimmermann M et al (2009) Favorable prognostic impact of NPM1 gene mutations in childhood acute myeloid leukemia, with emphasis on cytogenetically normal AML. Leukemia 23(2):262–270

    Article  CAS  PubMed  Google Scholar 

  • Hollink IHIM, van den Heuvel-Eibrink MM, Arentsen-Peters STCJM et al (2011) NUP98/NSD1 characterizes a novel poor prognostic group in acute myeloid leukemia with a distinct HOX gene expression pattern. Blood 118(13):3645–3656

    Article  CAS  PubMed  Google Scholar 

  • Hou H-A, Kuo Y-Y, Liu C-Y et al (2012) DNMT3A mutations in acute myeloid leukemia: stability during disease evolution and clinical implications. Blood 119(2):559–568

    Article  CAS  PubMed  Google Scholar 

  • How J, Sykes J, Gupta V et al (2012) Influence of FLT3-internal tandem duplication allele burden and white blood cell count on the outcome in patients with intermediate-risk karyotype acute myeloid leukemia. Cancer 118(24):6110–6117

    Article  CAS  PubMed  Google Scholar 

  • Hshieh TT, Jung WF, Grande LJ et al (2018) Prevalence of cognitive impairment and association with survival among older patients with hematologic cancers. JAMA Oncol 4(5):686–693

    Article  PubMed  PubMed Central  Google Scholar 

  • Huet S, Paubelle E, Lours C et al (2018) Validation of the prognostic value of the knowledge bank approach to determine AML prognosis in real life. Blood 132(8):865–867

    Article  CAS  PubMed  Google Scholar 

  • Hulegårdh E, Nilsson C, Lazarevic V et al (2015) Characterization and prognostic features of secondary acute myeloid leukemia in a population-based setting: a report from the Swedish acute Leukemia registry. Am J Hematol 90(3):208–214

    Article  PubMed  Google Scholar 

  • Hupfer V, Grishina O, Schmoor C et al (2018) Validation of a frailty score predicting survival of elderly, non-fit aml patients receiving hypomethylating therapy: results of the decider trial. Blood 132(Suppl 1):720

    Article  Google Scholar 

  • Illmer T, Schaich M, Ehninger G, Thiede C (2007) Tyrosine kinase mutations of JAK2 are rare events in AML but influence prognosis of patients with CBF-leukemias. Haematologica 92(1):137–138

    Article  PubMed  Google Scholar 

  • Inaba H, Zhou Y, Abla O et al (2015) Heterogeneous cytogenetic subgroups and outcomes in childhood acute megakaryoblastic leukemia: a retrospective international study. Blood 126(13):1575–1584

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • International Working Group for MDS Molecular Prognostic Committee, Haase D, Stevenson KE et al (2019) TP53 mutation status divides myelodysplastic syndromes with complex karyotypes into distinct prognostic subgroups. Leukemia 33(7):1747–1758

    Article  CAS  Google Scholar 

  • Ishikawa Y, Kawashima N, Atsuta Y et al (2020) Prospective evaluation of prognostic impact of KIT mutations on acute myeloid leukemia with RUNX1-RUNX1T1 and CBFB-MYH11. Blood Adv 4(1):66–75

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Itzykson R, Duployez N, Fasan A et al (2018a) Clonal interference of signaling mutations worsens prognosis in core-binding factor acute myeloid leukemia. Blood 132(2):187–196

    Article  CAS  PubMed  Google Scholar 

  • Itzykson R, Fournier E, Braun T et al (2018b) Oncogenic predictors of outcome in older AML patients treated intensively. Analysis of the ALFA-1200 trial. Blood 132(Suppl 1):993

    Article  Google Scholar 

  • Jost E, Lin Q, Weidner CI et al (2014) Epimutations mimic genomic mutations of DNMT3A in acute myeloid leukemia. Leukemia 28(6):1227–1234

    Article  CAS  PubMed  Google Scholar 

  • Jourdan E, Boissel N, Chevret S et al (2013) Prospective evaluation of gene mutations and minimal residual disease in patients with core binding factor acute myeloid leukemia. Blood 121(12):2213–2223

    Article  CAS  PubMed  Google Scholar 

  • Juliusson G, Antunovic P, Derolf Å et al (2009) Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry. Blood 113(18):4179–4187

    Article  CAS  PubMed  Google Scholar 

  • Juliusson G, Jädersten M, Deneberg S et al (2020) The prognostic impact of FLT3-ITD and NPM1 mutation in adult AML is age-dependent in the population-based setting. Blood Adv 4(6):1094–1101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jung N, Dai B, Gentles AJ, Majeti R, Feinberg AP (2015) An LSC epigenetic signature is largely mutation independent and implicates the HOXA cluster in AML pathogenesis. Nat Commun 6(1):1–12

    Article  Google Scholar 

  • Kadia TM, Jain P, Ravandi F et al (2016) TP53 mutations in newly diagnosed acute myeloid leukemia: clinicomolecular characteristics, response to therapy, and outcomes. Cancer 122(22):3484–3491

    Article  CAS  PubMed  Google Scholar 

  • Karakas T, Miething CC, Maurer U et al (2002) The coexpression of the apoptosis-related genes bcl-2 and wt1 in predicting survival in adult acute myeloid leukemia. Leukemia 16(5):846–854

    Article  CAS  PubMed  Google Scholar 

  • Kauer J, Schwartz K, Tandler C et al (2019) CD105 (Endoglin) as negative prognostic factor in AML. Sci Rep 9(1):1–11

    Article  CAS  Google Scholar 

  • Kayser S, Schlenk RF, Londono MC et al (2009) Insertion of FLT3 internal tandem duplication in the tyrosine kinase domain-1 is associated with resistance to chemotherapy and inferior outcome. Blood 114(12):2386–2392

    Article  CAS  PubMed  Google Scholar 

  • Kayser S, Döhner K, Krauter J et al (2011) The impact of therapy-related acute myeloid leukemia (AML) on outcome in 2853 adult patients with newly diagnosed AML. Blood 117(7):2137–2145

    Article  CAS  PubMed  Google Scholar 

  • Kayser S, Zucknick M, Döhner K et al (2012) Monosomal karyotype in adult acute myeloid leukemia: prognostic impact and outcome after different treatment strategies. Blood 119(2):551–558

    Article  CAS  PubMed  Google Scholar 

  • Kayser S, Elliott MA, Luskin M et al (2019) Characteristics and outcome of patients with core binding factor acute myeloid leukemia and FLT3-ITD: results from an international collaboration. Blood 134(Suppl_1):2693

    Article  Google Scholar 

  • Kihara R, Nagata Y, Kiyoi H et al (2014) Comprehensive analysis of genetic alterations and their prognostic impacts in adult acute myeloid leukemia patients. Leukemia 28(8):1586–1595

    Article  CAS  PubMed  Google Scholar 

  • Kim H-J, Ahn HK, Jung CW et al (2013) KIT D816 mutation associates with adverse outcomes in core binding factor acute myeloid leukemia, especially in the subgroup with RUNX1/RUNX1T1 rearrangement. Ann Hematol 92(2):163–171

    Article  CAS  PubMed  Google Scholar 

  • Kim Y, Lee GD, Park J et al (2015) Quantitative fragment analysis of FLT3-ITD efficiently identifying poor prognostic group with high mutant allele burden or long ITD length. Blood Cancer J 5(8):e336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kirkhus L, Jordhøy M, Šaltytė Benth J et al (2016) Comparing comorbidity scales: attending physician score versus the cumulative illness rating scale for geriatrics. J Geriatr Oncol 7(2):90–98

    Article  PubMed  Google Scholar 

  • Kiyoi H, Naoe T, Nakano Y et al (1999) Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia. Blood 93(9):3074–3080

    CAS  PubMed  Google Scholar 

  • Klein K, Kaspers G, Harrison CJ et al (2015) Clinical impact of additional cytogenetic aberrations, cKIT and RAS mutations, and treatment elements in Pediatric t(8;21)-AML: results from an international retrospective study by the International Berlin-Frankfurt-Münster Study group. J Clin Oncol 33(36):4247–4258

    Article  PubMed  PubMed Central  Google Scholar 

  • Klepin HD, Geiger AM, Tooze JA et al (2013) Geriatric assessment predicts survival for older adults receiving induction chemotherapy for acute myelogenous leukemia. Blood 121(21):4287–4294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kobayashi R, Tawa A, Hanada R et al (2007) Extramedullary infiltration at diagnosis and prognosis in children with acute myelogenous leukemia. Pediatr Blood Cancer 48(4):393–398

    Article  PubMed  Google Scholar 

  • Konstandin NP, Pastore F, Herold T et al (2018) Genetic heterogeneity of cytogenetically normal AML with mutations of CEBPA. Blood Adv 2(20):2724–2731

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kornblau SM, Womble M, Qiu YH et al (2006) Simultaneous activation of multiple signal transduction pathways confers poor prognosis in acute myelogenous leukemia. Blood 108(7):2358–2365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kornblau SM, Tibes R, Qiu YH et al (2009) Functional proteomic profiling of AML predicts response and survival. Blood 113(1):154–164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kornblau SM, Singh N, Qiu Y et al (2010a) Highly phosphorylated FOXO3A is an adverse prognostic factor in acute myeloid leukemia. Clin Cancer Res 16(6):1865–1874

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kornblau SM, McCue D, Singh N et al (2010b) Recurrent expression signatures of cytokines and chemokines are present and are independently prognostic in acute myelogenous leukemia and myelodysplasia. Blood 116(20):4251–4261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kornblau SM, Qiu YH, Zhang N et al (2011) Abnormal expression of FLI1 protein is an adverse prognostic factor in acute myeloid leukemia. Blood 118(20):5604–5612

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kottaridis PD, Gale RE, Frew ME et al (2001) The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood 98(6):1752–1759

    Article  CAS  PubMed  Google Scholar 

  • Krauth M-T, Eder C, Alpermann T et al (2014) High number of additional genetic lesions in acute myeloid leukemia with t(8;21)/RUNX1-RUNX1T1: frequency and impact on clinical outcome. Leukemia 28(7):1449–1458

    Article  CAS  PubMed  Google Scholar 

  • Kroeze LI, Aslanyan MG, van Rooij A et al (2014) Characterization of acute myeloid leukemia based on levels of global hydroxymethylation. Blood 124(7):1110–1118

    Article  CAS  PubMed  Google Scholar 

  • Kusec R, Jaksic O, Ostojic S et al (2006) More on prognostic significance of FLT3/ITD size in acute myeloid leukemia (AML). Blood 108(1):405–406

    Article  CAS  PubMed  Google Scholar 

  • Kuykendall A, Duployez N, Boissel N, Lancet JE, Welch JS (2018) Acute myeloid Leukemia: the good, the bad, and the ugly. Am Soc Clin Oncol Educ Book 38:555–573

    Article  PubMed  Google Scholar 

  • Lad D, Jain A, Varma S (2017) Complications and management of coagulation disorders in leukemia patients. Blood Lymphat Cancer 7:61–72

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lancet JE, Uy GL, Cortes JE et al (2016) Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML. JCO 34(15_suppl):7000

    Article  Google Scholar 

  • Langer C, Radmacher MD, Ruppert AS et al (2008) High BAALC expression associates with other molecular prognostic markers, poor outcome, and a distinct gene-expression signature in cytogenetically normal patients younger than 60 years with acute myeloid leukemia: a Cancer and Leukemia Group B (CALGB) study. Blood 111(11):5371–5379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Langer C, Marcucci G, Holland KB et al (2009) Prognostic importance of MN1 transcript levels, and biologic insights from MN1-associated gene and microRNA expression signatures in cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. J Clin Oncol 27(19):3198–3204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Laupeze B, Amiot L, Drenou B et al (2002) High multidrug resistance protein activity in acute myeloid leukaemias is associated with poor response to chemotherapy and reduced patient survival. Br J Haematol 116(4):834–838

    Article  CAS  PubMed  Google Scholar 

  • Lauria F, Raspadori D, Rondelli D et al (1997) High bcl-2 expression in acute myeloid leukemia cells correlates with CD34 positivity and complete remission rate. Leukemia 11(12):2075–2078

    Article  CAS  PubMed  Google Scholar 

  • Lavallée V-P, Krosl J, Lemieux S et al (2016) Chemo-genomic interrogation of CEBPA mutated AML reveals recurrent CSF3R mutations and subgroup sensitivity to JAK inhibitors. Blood 127(24):3054–3061

    Article  PubMed  CAS  Google Scholar 

  • Lazarevic V, Hörstedt A-S, Johansson B et al (2014) Incidence and prognostic significance of karyotypic subgroups in older patients with acute myeloid leukemia: the Swedish population-based experience. Blood Cancer J 4(2):e188–e188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lazarevic V, Rosso A, Juliusson G et al (2015) Prognostic significance of high hyperdiploid and triploid/tetraploid adult acute myeloid leukemia. Am J Hematol 90(9):800–805

    Article  CAS  PubMed  Google Scholar 

  • Lazarevic VL, Labopin M, Depei W et al (2018) Relatively favorable outcome after allogeneic stem cell transplantation for BCR-ABL1-positive AML: a survey from the acute leukemia working party of the European Society for Blood and Marrow Transplantation (EBMT). Am J Hematol 93(1):31–39

    Article  CAS  PubMed  Google Scholar 

  • Lazenby M, Gilkes AF, Marrin C et al (2014) The prognostic relevance of flt3 and npm1 mutations on older patients treated intensively or non-intensively: a study of 1312 patients in the UK NCRI AML16 trial. Leukemia 28(10):1953–1959

    Article  CAS  PubMed  Google Scholar 

  • Legrand O, Simonin G, Perrot JY, Zittoun R, Marie JP (1998) Pgp and MRP activities using calcein-AM are prognostic factors in adult acute myeloid leukemia patients. Blood 91(12):4480–4488

    Article  CAS  PubMed  Google Scholar 

  • Leith CP, Kopecky KJ, Godwin J et al (1997) Acute myeloid leukemia in the elderly: assessment of multidrug resistance (MDR1) and cytogenetics distinguishes biologic subgroups with remarkably distinct responses to standard chemotherapy. A Southwest Oncology Group study. Blood 89(9):3323–3329

    Article  CAS  PubMed  Google Scholar 

  • Leith CP, Kopecky KJ, Chen IM et al (1999) Frequency and clinical significance of the expression of the multidrug resistance proteins MDR1/P-glycoprotein, MRP1, and LRP in acute myeloid leukemia: a Southwest Oncology Group study. Blood 94(3):1086–1099

    CAS  PubMed  Google Scholar 

  • Levine JH, Simonds EF, Bendall SC et al (2015) Data-driven phenotypic dissection of AML reveals progenitor-like cells that correlate with prognosis. Cell 162(1):184–197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ley TJ, Ding L, Walter MJ et al (2010) DNMT3A mutations in acute myeloid leukemia. N Engl J Med 363(25):2424–2433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Z, Herold T, He C et al (2013) Identification of a 24-gene prognostic signature that improves the European LeukemiaNet risk classification of acute myeloid leukemia: an international collaborative study. J Clin Oncol 31(9):1172–1181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li H-Y, Deng D-H, Huang Y et al (2015) Favorable prognosis of biallelic CEBPA gene mutations in acute myeloid leukemia patients: a meta-analysis. Eur J Haematol 94(5):439–448

    Article  CAS  PubMed  Google Scholar 

  • Li S, Garrett-Bakelman FE, Chung SS et al (2016) Distinct evolution and dynamics of epigenetic and genetic heterogeneity in acute myeloid leukemia. Nat Med 22(7):792–799

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin T-C, Hou H-A, Chou W-C et al (2011) CEBPA methylation as a prognostic biomarker in patients with de novo acute myeloid leukemia. Leukemia 25(1):32–40

    Article  CAS  PubMed  Google Scholar 

  • Linch DC, Hills RK, Burnett AK, Khwaja A, Gale RE (2014) Impact of FLT3(ITD) mutant allele level on relapse risk in intermediate-risk acute myeloid leukemia. Blood 124(2):273–276

    Article  CAS  PubMed  Google Scholar 

  • Linch DC, Hills RK, Burnett AK, Russell N, Gale RE (2020) Analysis of the clinical impact of NPM1 mutant allele burden in a large cohort of younger adult patients with acute myeloid leukaemia. Br J Haematol 188(6):852–859

    Article  CAS  PubMed  Google Scholar 

  • Lindsley RC, Mar BG, Mazzola E et al (2015) Acute myeloid leukemia ontogeny is defined by distinct somatic mutations. Blood 125(9):1367–1376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu S-B, Dong H-J, Bao X-B et al (2019) Impact of FLT3-ITD length on prognosis of acute myeloid leukemia. Haematologica 104(1):e9–e12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Loghavi S, Zuo Z, Ravandi F et al (2014) Clinical features of de novo acute myeloid leukemia with concurrent DNMT3A, FLT3 and NPM1 mutations. J Hematol Oncol 7(1):74

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lugthart S, van Drunen E, van Norden Y et al (2008) High EVI1 levels predict adverse outcome in acute myeloid leukemia: prevalence of EVI1 overexpression and chromosome 3q26 abnormalities underestimated. Blood 111(8):4329–4337

    Article  CAS  PubMed  Google Scholar 

  • Lugthart S, Gröschel S, Beverloo HB et al (2010) Clinical, molecular, and prognostic significance of WHO type inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and various other 3q abnormalities in acute myeloid leukemia. J Clin Oncol 28(24):3890–3898

    Article  PubMed  Google Scholar 

  • Luskin MR, Gimotty PA, Smith C et al (2016) A clinical measure of DNA methylation predicts outcome in de novo acute myeloid leukemia. JCI Insight 1(9):e87323

    Article  PubMed  PubMed Central  Google Scholar 

  • Ma Z, Morris SW, Valentine V et al (2001) Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia. Nat Genet 28(3):220–221

    Article  CAS  PubMed  Google Scholar 

  • Malagola M, Skert C, Vignetti M et al (2011) A simple prognostic scoring system for newly diagnosed cytogenetically normal acute myeloid leukemia: retrospective analysis of 530 patients. Leuk Lymphoma 52(12):2329–2335

    Article  PubMed  Google Scholar 

  • Maley CC, Aktipis A, Graham TA et al (2017) Classifying the evolutionary and ecological features of neoplasms. Nat Rev Cancer 17(10):605–619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Manara E, Basso G, Zampini M et al (2017) Characterization of children with FLT3-ITD acute myeloid leukemia: a report from the AIEOP AML-2002 Study Group. Leukemia 31(1):18–25

    Article  CAS  PubMed  Google Scholar 

  • Marceau-Renaut A, Guihard S, Castaigne S et al (2015) Classification of CEBPA mutated acute myeloid leukemia by GATA2 mutations. Am J Hematol 90(5):E93–E94

    Article  CAS  PubMed  Google Scholar 

  • Marceau-Renaut A, Duployez N, Ducourneau B et al (2018) Molecular profiling defines distinct prognostic subgroups in childhood AML: a report from the French ELAM02 study group. HemaSphere 2(1):e31

    Article  PubMed  PubMed Central  Google Scholar 

  • Marcucci G, Mrózek K, Ruppert AS et al (2005a) Prognostic factors and outcome of core binding factor acute myeloid leukemia patients with t(8;21) differ from those of patients with inv(16): a Cancer and Leukemia Group B study. J Clin Oncol 23(24):5705–5717

    Article  PubMed  Google Scholar 

  • Marcucci G, Baldus CD, Ruppert AS et al (2005b) Overexpression of the ETS-related gene, ERG, predicts a worse outcome in acute myeloid leukemia with normal karyotype: a Cancer and Leukemia Group B study. J Clin Oncol 23(36):9234–9242

    Article  CAS  PubMed  Google Scholar 

  • Marcucci G, Maharry K, Whitman SP et al (2007) High expression levels of the ETS-related gene, ERG, predict adverse outcome and improve molecular risk-based classification of cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. J Clin Oncol 25(22):3337–3343

    Article  CAS  PubMed  Google Scholar 

  • Marcucci G, Radmacher MD, Maharry K et al (2008) MicroRNA expression in cytogenetically normal acute myeloid leukemia. N Engl J Med 358(18):1919–1928

    Article  CAS  PubMed  Google Scholar 

  • Marcucci G, Maharry K, Wu Y-Z et al (2010) IDH1 and IDH2 gene mutations identify novel molecular subsets within de novo cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. J Clin Oncol 28(14):2348–2355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marcucci G, Metzeler KH, Schwind S et al (2012) Age-related prognostic impact of different types of DNMT3A mutations in adults with primary cytogenetically normal acute myeloid leukemia. J Clin Oncol 30(7):742–750

    Article  PubMed  PubMed Central  Google Scholar 

  • Marcucci G, Maharry KS, Metzeler KH et al (2013) Clinical role of microRNAs in cytogenetically normal acute myeloid leukemia: miR-155 upregulation independently identifies high-risk patients. J Clin Oncol 31(17):2086–2093

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marcucci G, Yan P, Maharry K et al (2014) Epigenetics meets genetics in acute myeloid leukemia: clinical impact of a novel seven-gene score. J Clin Oncol 32(6):548–556

    Article  PubMed  Google Scholar 

  • Märklin M, Hagelstein I, Hinterleitner C et al (2020) CD105 (Endoglin) as risk marker in AML patients undergoing stem cell transplantation. Int J Hematol 112(1):57–64

    Article  PubMed  CAS  Google Scholar 

  • Masetti R, Bertuccio SN, Pession A, Locatelli F (2019) CBFA2T3-GLIS2-positive acute myeloid leukaemia. A peculiar paediatric entity. Br J Haematol 184(3):337–347

    Article  CAS  PubMed  Google Scholar 

  • Mason KD, Juneja SK, Szer J (2006) The immunophenotype of acute myeloid leukemia: is there a relationship with prognosis? Blood Rev 20(2):71–82

    Article  CAS  PubMed  Google Scholar 

  • Mead AJ, Linch DC, Hills RK et al (2007) FLT3 tyrosine kinase domain mutations are biologically distinct from and have a significantly more favorable prognosis than FLT3 internal tandem duplications in patients with acute myeloid leukemia. Blood 110(4):1262–1270

    Article  CAS  PubMed  Google Scholar 

  • Medeiros BC, Othus M, Fang M, Roulston D, Appelbaum FR (2010) Prognostic impact of monosomal karyotype in young adult and elderly acute myeloid leukemia: the southwest oncology group (SWOG) experience. Blood 116(13):2224–2228

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Medeiros BC, Othus M, Fang M, Appelbaum FR, Erba HP (2015) Cytogenetic heterogeneity negatively impacts outcomes in patients with acute myeloid leukemia. Haematologica 100(3):331–335

    Article  PubMed  PubMed Central  Google Scholar 

  • Mendler JH, Maharry K, Radmacher MD et al (2012) RUNX1 mutations are associated with poor outcome in younger and older patients with cytogenetically normal acute myeloid leukemia and with distinct gene and MicroRNA expression signatures. J Clin Oncol 30(25):3109–3118

    Article  PubMed  PubMed Central  Google Scholar 

  • Meshinchi S, Alonzo TA, Stirewalt DL et al (2006) Clinical implications of FLT3 mutations in pediatric AML. Blood 108(12):3654–3661

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Metzeler KH, Hummel M, Bloomfield CD et al (2008) An 86-probe-set gene-expression signature predicts survival in cytogenetically normal acute myeloid leukemia. Blood 112(10):4193–4201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Metzeler KH, Dufour A, Benthaus T et al (2009) ERG expression is an independent prognostic factor and allows refined risk stratification in cytogenetically normal acute myeloid leukemia: a comprehensive analysis of ERG, MN1, and BAALC transcript levels using oligonucleotide microarrays. J Clin Oncol 27(30):5031–5038

    Article  CAS  PubMed  Google Scholar 

  • Metzeler KH, Becker H, Maharry K et al (2011a) ASXL1 mutations identify a high-risk subgroup of older patients with primary cytogenetically normal AML within the ELN favorable genetic category. Blood 118(26):6920–6929

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Metzeler KH, Maharry K, Radmacher MD et al (2011b) TET2 mutations improve the new European LeukemiaNet risk classification of acute myeloid leukemia: a Cancer and Leukemia Group B study. J Clin Oncol 29(10):1373–1381

    Article  PubMed  PubMed Central  Google Scholar 

  • Metzeler KH, Herold T, Rothenberg-Thurley M et al (2016) Spectrum and prognostic relevance of driver gene mutations in acute myeloid leukemia. Blood 128(5):686–698

    Article  CAS  PubMed  Google Scholar 

  • Meyer C, Burmeister T, Gröger D et al (2018) The MLL recombinome of acute leukemias in 2017. Leukemia 32(2):273–284

    Article  CAS  PubMed  Google Scholar 

  • Micol JB, Boissel N, Renneville A et al (2009) The role of cytogenetic abnormalities in acute myeloid leukemia with NPM1 mutations and no FLT3 internal tandem duplication. Blood 114(20):4601–4602

    Article  CAS  PubMed  Google Scholar 

  • Middeke JM, Herold S, Rücker-Braun E et al (2016) TP53 mutation in patients with high-risk acute myeloid leukaemia treated with allogeneic haematopoietic stem cell transplantation. Br J Haematol 172(6):914–922

    Article  CAS  PubMed  Google Scholar 

  • Minetto P, Guolo F, Clavio M et al (2018) A blastic plasmacytoid dendritic cell neoplasm-like phenotype identifies a subgroup of npm1-mutated acute myeloid leukemia patients with worse prognosis. Am J Hematol 93(2):E33–E35

    Article  PubMed  Google Scholar 

  • Moison C, Lavallée V-P, Thiollier C et al (2019) Complex karyotype AML displays G2/M signature and hypersensitivity to PLK1 inhibition. Blood Adv 3(4):552–563

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Montesinos P, Lorenzo I, Martín G et al (2008) Tumor lysis syndrome in patients with acute myeloid leukemia: identification of risk factors and development of a predictive model. Haematologica 93(1):67 LP–74 LP

    Article  CAS  Google Scholar 

  • Montesinos P, Bergua J, Infante J et al (2019) Update on management and progress of novel therapeutics for R/R AML: an Iberian expert panel consensus. Ann Hematol 98(11):2467–2483

    Article  PubMed  Google Scholar 

  • Mosna F, Papayannidis C, Martinelli G et al (2015) Complex karyotype, older age, and reduced first-line dose intensity determine poor survival in core binding factor acute myeloid leukemia patients with long-term follow-up. Am J Hematol 90(6):515–523

    Article  CAS  PubMed  Google Scholar 

  • Mrózek K, Heinonen K, Lawrence D et al (1997) Adult patients with de novo acute myeloid leukemia and t(9; 11)(p22; q23) have a superior outcome to patients with other translocations involving band 11q23: a Cancer and Leukemia Group B study. Blood 90(11):4532–4538

    Article  PubMed  Google Scholar 

  • Mrózek K, Marcucci G, Nicolet D et al (2012) Prognostic significance of the European LeukemiaNet standardized system for reporting cytogenetic and molecular alterations in adults with acute myeloid leukemia. J Clin Oncol 30(36):4515–4523

    Article  PubMed  PubMed Central  Google Scholar 

  • Mrózek K, Eisfeld A-K, Kohlschmidt J et al (2019) Complex karyotype in de novo acute myeloid leukemia: typical and atypical subtypes differ molecularly and clinically. Leukemia 33(7):1620–1634

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nagel G, Weber D, Fromm E et al (2017) Epidemiological, genetic, and clinical characterization by age of newly diagnosed acute myeloid leukemia based on an academic population-based registry study (AMLSG BiO). Ann Hematol 96(12):1993–2003

    Article  PubMed  PubMed Central  Google Scholar 

  • Nahi H, Lehmann S, Bengtzen S et al (2008) Chromosomal aberrations in 17p predict in vitro drug resistance and short overall survival in acute myeloid leukemia. Leuk Lymphoma 49(3):508–516

    Article  CAS  PubMed  Google Scholar 

  • Nakao M, Yokota S, Iwai T et al (1996) Internal tandem duplication of the flt3 gene found in acute myeloid leukemia. Leukemia 10(12):1911–1918

    CAS  PubMed  Google Scholar 

  • Nakase K, Kita K, Kageyama S et al (1997) Clinical importance of interleukin-2 receptor alpha-chain expression in acute leukemia. The Japan Cooperative Group of Leukemia/Lymphoma. Cancer Detect Prev 21(3):273–279

    CAS  PubMed  Google Scholar 

  • Neuendorff NR, Burmeister T, Dörken B, Westermann J (2016) BCR-ABL-positive acute myeloid leukemia: a new entity? Analysis of clinical and molecular features. Ann Hematol 95(8):1211–1221

    Article  CAS  PubMed  Google Scholar 

  • Neuendorff NR, Hemmati P, Arnold R et al (2018) BCR-ABL+ acute myeloid leukemia: are we always dealing with a high-risk disease? Blood Adv 2(12):1409–1411

    Article  PubMed  PubMed Central  Google Scholar 

  • Ng SWK, Mitchell A, Kennedy JA et al (2016) A 17-gene stemness score for rapid determination of risk in acute leukaemia. Nature 540(7633):433–437

    Article  CAS  PubMed  Google Scholar 

  • Nguyen L, Zhang X, Roberts E et al (2020) Comparison of mutational profiles and clinical outcomes in patients with acute myeloid leukemia with mutated RUNX1 versus acute myeloid leukemia with myelodysplasia-related changes with mutated RUNX1. Leuk Lymphoma 61(6):1395–1405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nibourel O, Kosmider O, Cheok M et al (2010) Incidence and prognostic value of TET2 alterations in de novo acute myeloid leukemia achieving complete remission. Blood 116(7):1132–1135

    Article  CAS  PubMed  Google Scholar 

  • Nibourel O, Guihard S, Roumier C et al (2017) Copy-number analysis identified new prognostic marker in acute myeloid leukemia. Leukemia 31(3):555–564

    Article  CAS  PubMed  Google Scholar 

  • Noort S, Zimmermann M, Reinhardt D et al (2018) Prognostic impact of t(16;21)(p11;q22) and t(16;21)(q24;q22) in pediatric AML: a retrospective study by the I-BFM study group. Blood 132(15):1584–1592

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Noort S, Wander P, Alonzo TA et al (2021) The clinical and biological characteristics of NUP98-KDM5A in pediatric acute myeloid leukemia. Haematologica 106(2):630–634

    Article  PubMed  Google Scholar 

  • Ok CY, Patel KP, Garcia-Manero G et al (2015) TP53 mutation characteristics in therapy-related myelodysplastic syndromes and acute myeloid leukemia is similar to de novo diseases. J Hematol Oncol 8:45

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ong YL, McMullin MF, Bailie KE et al (2000) High bax expression is a good prognostic indicator in acute myeloid leukaemia. Br J Haematol 111(1):182–189

    CAS  PubMed  Google Scholar 

  • Opatz S, Bamopoulos SA, Metzeler KH et al (2020) The clinical mutatome of core binding factor leukemia. Leukemia:1–10

    Google Scholar 

  • Ossenkoppele G, Montesinos P (2019) Challenges in the diagnosis and treatment of secondary acute myeloid leukemia. Crit Rev Oncol Hematol 138:6–13

    Article  PubMed  Google Scholar 

  • Ostronoff F, Othus M, Gerbing RB et al (2014) NUP98/NSD1 and FLT3/ITD coexpression is more prevalent in younger AML patients and leads to induction failure: a COG and SWOG report. Blood 124(15):2400–2407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ostronoff F, Othus M, Lazenby M et al (2015) Prognostic significance of NPM1 mutations in the absence of FLT3-internal tandem duplication in older patients with acute myeloid leukemia: a SWOG and UK National Cancer Research Institute/Medical Research Council report. J Clin Oncol 33(10):1157–1164

    Article  PubMed  PubMed Central  Google Scholar 

  • Ottema S, Mulet-Lazaro R, Beverloo HB et al (2020) Atypical 3q26/MECOM rearrangements genocopy inv(3)/t(3;3) in acute myeloid leukemia. Blood 136(2):224–234

    Article  PubMed  Google Scholar 

  • Pabst T, Mueller BU, Zhang P et al (2001) Dominant-negative mutations of CEBPA, encoding CCAAT/enhancer binding protein-alpha (C/EBPalpha), in acute myeloid leukemia. Nat Genet 27(3):263–270

    Article  CAS  PubMed  Google Scholar 

  • Pabst T, Eyholzer M, Fos J, Mueller BU (2009) Heterogeneity within AML with CEBPA mutations; only CEBPA double mutations, but not single CEBPA mutations are associated with favourable prognosis. Br J Cancer 100(8):1343–1346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Papaemmanuil E, Gerstung M, Bullinger L et al (2016) Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med 374(23):2209–2221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park SH, Chi H-S, Min S-K et al (2011) Prognostic impact of c-KIT mutations in core binding factor acute myeloid leukemia. Leuk Res 35(10):1376–1383

    Article  CAS  PubMed  Google Scholar 

  • Paschka P, Marcucci G, Ruppert AS et al (2006) Adverse prognostic significance of KIT mutations in adult acute myeloid leukemia with inv(16) and t(8;21): a Cancer and Leukemia Group B study. J Clin Oncol 24(24):3904–3911

    Article  CAS  PubMed  Google Scholar 

  • Paschka P, Marcucci G, Ruppert AS et al (2008) Wilms’ tumor 1 gene mutations independently predict poor outcome in adults with cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. J Clin Oncol 26(28):4595–4602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paschka P, Schlenk RF, Gaidzik VI et al (2010) IDH1 and IDH2 mutations are frequent genetic alterations in acute myeloid leukemia and confer adverse prognosis in cytogenetically normal acute myeloid leukemia with NPM1 mutation without FLT3 internal tandem duplication. J Clin Oncol 28(22):3636–3643

    Article  CAS  PubMed  Google Scholar 

  • Paschka P, Du J, Schlenk RF et al (2013) Secondary genetic lesions in acute myeloid leukemia with inv(16) or t(16;16): a study of the German-Austrian AML study group (AMLSG). Blood 121(1):170–177

    Article  CAS  PubMed  Google Scholar 

  • Paschka P, Schlenk RF, Gaidzik VI et al (2015) ASXL1 mutations in younger adult patients with acute myeloid leukemia: a study by the German-Austrian Acute Myeloid Leukemia Study Group. Haematologica 100(3):324–330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pastore F, Kling D, Hoster E et al (2014a) Long-term follow-up of cytogenetically normal CEBPA-mutated AML. J Hematol Oncol 7(1):55

    Article  PubMed  PubMed Central  Google Scholar 

  • Pastore F, Dufour A, Benthaus T et al (2014b) Combined molecular and clinical prognostic index for relapse and survival in cytogenetically normal acute myeloid leukemia. J Clin Oncol 32(15):1586–1594

    Article  PubMed  PubMed Central  Google Scholar 

  • Patel JP, Gönen M, Figueroa ME et al (2012) Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med 366(12):1079–1089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patel SS, Kuo FC, Gibson CJ et al (2018) High NPM1-mutant allele burden at diagnosis predicts unfavorable outcomes in de novo AML. Blood 131(25):2816–2825

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patkar N, Shaikh AF, Kakirde C et al (2019) A novel machine-learning-derived genetic score correlates with measurable residual disease and is highly predictive of outcome in acute myeloid leukemia with mutated NPM1. Blood Cancer J 9(10):1–4

    Article  Google Scholar 

  • Perry M, Bertoli S, Rocher C et al (2018) FLT3-TKD mutations associated with NPM1 mutations define a favorable-risk group in patients with acute myeloid Leukemia. Clin Lymph Myeloma Leukemia 18(12):e545–e550

    Article  Google Scholar 

  • Peterlin P, Renneville A, Abdelali RB et al (2015) Impact of additional genetic alterations on the outcome of patients with NPM1-mutated cytogenetically normal acute myeloid leukemia. Haematologica 100(5):e196–e199

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pigneux A, Labopin M, Maertens J et al (2015) Outcome of allogeneic hematopoietic stem-cell transplantation for adult patients with AML and 11q23/MLL rearrangement (MLL-r AML). Leukemia 29(12):2375–2381

    Article  CAS  PubMed  Google Scholar 

  • Pirker R, Wallner J, Geissler K et al (1991) MDR1 gene expression and treatment outcome in acute myeloid leukemia. J Natl Cancer Inst 83(10):708–712

    Article  CAS  PubMed  Google Scholar 

  • Poiré X, Labopin M, Polge E et al (2020) The impact of concomitant cytogenetic abnormalities on acute myeloid leukemia with monosomy 7 or deletion 7q after HLA-matched allogeneic stem cell transplantation. Am J Hematol 95(3):282–294

    Article  PubMed  CAS  Google Scholar 

  • Ponziani V, Gianfaldoni G, Mannelli F et al (2006) The size of duplication does not add to the prognostic significance of FLT3 internal tandem duplication in acute myeloid leukemia patients. Leukemia 20(11):2074–2076

    Article  CAS  PubMed  Google Scholar 

  • Port M, Böttcher M, Thol F et al (2014) Prognostic significance of FLT3 internal tandem duplication, nucleophosmin 1, and CEBPA gene mutations for acute myeloid leukemia patients with normal karyotype and younger than 60 years: a systematic review and meta-analysis. Ann Hematol 93(8):1279–1286

    Article  CAS  PubMed  Google Scholar 

  • Prassek VV, Rothenberg-Thurley M, Sauerland MC et al (2018) Genetics of acute myeloid leukemia in the elderly: mutation spectrum and clinical impact in intensively treated patients aged 75 years or older. Haematologica 103(11):1853–1861

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pratcorona M, Abbas S, Sanders MA et al (2012) Acquired mutations in ASXL1 in acute myeloid leukemia: prevalence and prognostic value. Haematologica 97(3):388–392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pratcorona M, Brunet S, Nomdedéu J et al (2013) Favorable outcome of patients with acute myeloid leukemia harboring a low-allelic burden FLT3-ITD mutation and concomitant NPM1 mutation: relevance to post-remission therapy. Blood 121(14):2734–2738

    Article  CAS  PubMed  Google Scholar 

  • Pratz KW, Levis M (2017) How I treat FLT3-mutated AML. Blood 129(5):565–571

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prébet T, Boissel N, Reutenauer S et al (2009) Acute myeloid leukemia with translocation (8;21) or inversion (16) in elderly patients treated with conventional chemotherapy: a collaborative study of the French CBF-AML Intergroup. J Clin Oncol 27(28):4747–4753

    Article  PubMed  Google Scholar 

  • Preudhomme C, Sagot C, Boissel N et al (2002) Favorable prognostic significance of CEBPA mutations in patients with de novo acute myeloid leukemia: a study from the Acute Leukemia French Association (ALFA). Blood 100(8):2717–2723

    Article  CAS  PubMed  Google Scholar 

  • Prochazka KT, Pregartner G, Rücker FG et al (2019) Clinical implications of subclonal TP53 mutations in acute myeloid leukemia. Haematologica 104(3):516–523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pulte D, Jansen L, Castro FA et al (2016) Survival in patients with acute myeloblastic leukemia in Germany and the United States: major differences in survival in young adults. Int J Cancer 139(6):1289–1296

    Article  CAS  PubMed  Google Scholar 

  • Qin Y-Z, Zhu H-H, Jiang Q et al (2014) Prevalence and prognostic significance of c-KIT mutations in core binding factor acute myeloid leukemia: a comprehensive large-scale study from a single Chinese center. Leuk Res 38(12):1435–1440

    Article  CAS  PubMed  Google Scholar 

  • Qin T, Wu S, Zhao H et al (2017) Molecular predictors of post-transplant survival in acute myeloid leukemia. Blood Cancer J 7(12):1–5

    Article  Google Scholar 

  • Quesada AE, Montalban-Bravo G, Luthra R et al (2020) Clinico-pathologic characteristics and outcomes of the World Health Organization (WHO) provisional entity de novo acute myeloid leukemia with mutated RUNX1. Mod Pathol 33(9):1678–1689

    Article  CAS  PubMed  Google Scholar 

  • Renneville A, Boissel N, Gachard N et al (2009a) The favorable impact of CEBPA mutations in patients with acute myeloid leukemia is only observed in the absence of associated cytogenetic abnormalities and FLT3 internal duplication. Blood 113(21):5090–5093

    Article  CAS  PubMed  Google Scholar 

  • Renneville A, Boissel N, Zurawski V et al (2009b) Wilms tumor 1 gene mutations are associated with a higher risk of recurrence in young adults with acute myeloid leukemia: a study from the Acute Leukemia French Association. Cancer 115(16):3719–3727

    Article  CAS  PubMed  Google Scholar 

  • Renneville A, Boissel N, Nibourel O et al (2012) Prognostic significance of DNA methyltransferase 3A mutations in cytogenetically normal acute myeloid leukemia: a study by the Acute Leukemia French Association. Leukemia 26(6):1247–1254

    Article  CAS  PubMed  Google Scholar 

  • Repp R, Schaekel U, Helm G et al (2003) Immunophenotyping is an independent factor for risk stratification in AML. Cytometry B Clin Cytom 53(1):11–19

    Article  CAS  PubMed  Google Scholar 

  • Ribeiro AFT, Pratcorona M, Erpelinck-Verschueren C et al (2012) Mutant DNMT3A: a marker of poor prognosis in acute myeloid leukemia. Blood 119(24):5824–5831

    Google Scholar 

  • Riera L, Marmont F, Toppino D et al (2013) Core binding factor acute myeloid leukaemia and c-KIT mutations. Oncol Rep 29(5):1867–1872

    Article  CAS  PubMed  Google Scholar 

  • Rockova V, Abbas S, Wouters BJ et al (2011) Risk stratification of intermediate-risk acute myeloid leukemia: integrative analysis of a multitude of gene mutation and gene expression markers. Blood 118(4):1069–1076

    Article  CAS  PubMed  Google Scholar 

  • Röllig C, Bornhäuser M, Thiede C et al (2011) Long-term prognosis of acute myeloid Leukemia according to the new genetic risk classification of the European LeukemiaNet recommendations: evaluation of the proposed reporting system. JCO 29(20):2758–2765

    Article  Google Scholar 

  • Rozovski U, Ohanian M, Ravandi F et al (2015) Incidence of and risk factors for involvement of the central nervous system in acute myeloid leukemia. Leuk Lymphoma 56(5):1392–1397

    Article  CAS  PubMed  Google Scholar 

  • Rücker FG, Schlenk RF, Bullinger L et al (2012) TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome. Blood 119(9):2114–2121

    Article  PubMed  CAS  Google Scholar 

  • Rücker FG, Agrawal M, Corbacioglu A et al (2019) Measurable residual disease monitoring in acute myeloid leukemia with t(8;21)(q22;q22.1): results from the AML Study Group. Blood 134(19):1608–1618

    Article  PubMed  Google Scholar 

  • Sakaguchi M, Yamaguchi H, Najima Y et al (2018) Prognostic impact of low allelic ratio FLT3-ITD and NPM1 mutation in acute myeloid leukemia. Blood Adv 2(20):2744–2754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sandahl JD, Coenen EA, Forestier E et al (2014) t(6;9)(p22;q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an international study of 62 patients. Haematologica 99(5):865–872

    Article  PubMed  PubMed Central  Google Scholar 

  • Santos FPS, Jones D, Qiao W et al (2011) Prognostic value of FLT3 mutations among different cytogenetic subgroups in acute myeloid leukemia. Cancer 117(10):2145–2155

    Article  CAS  PubMed  Google Scholar 

  • Sanz MA, Fenaux P, Tallman MS et al (2019) Management of acute promyelocytic leukemia: updated recommendations from an expert panel of the European LeukemiaNet. Blood 133(15):1630–1643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sasaki K, Kanagal-Shamanna R, Montalban-Bravo G et al (2020) Impact of the variant allele frequency of ASXL1, DNMT3A, JAK2, TET2, TP53, and NPM1 on the outcomes of patients with newly diagnosed acute myeloid leukemia. Cancer 126(4):765–774

    Article  CAS  PubMed  Google Scholar 

  • Schanz J, Tüchler H, Solé F et al (2012) New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge. J Clin Oncol 30(8):820–829

    Article  PubMed  PubMed Central  Google Scholar 

  • Schellongowski P, Staudinger T, Kundi M et al (2011) Prognostic factors for intensive care unit admission, intensive care outcome, and post-intensive care survival in patients with de novo acute myeloid leukemia: a single center experience. Haematologica 96(2):231–237

    Article  PubMed  Google Scholar 

  • Schlenk RF, Benner A, Krauter J et al (2004) Individual patient data-based meta-analysis of patients aged 16 to 60 years with core binding factor acute myeloid leukemia: a survey of the German Acute Myeloid Leukemia Intergroup. J Clin Oncol 22(18):3741–3750

    Article  CAS  PubMed  Google Scholar 

  • Schlenk RF, Döhner K, Krauter J et al (2008) Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med 358(18):1909–1918

    Article  CAS  PubMed  Google Scholar 

  • Schlenk RF, Taskesen E, van Norden Y et al (2013) The value of allogeneic and autologous hematopoietic stem cell transplantation in prognostically favorable acute myeloid leukemia with double mutant CEBPA. Blood 122(9):1576–1582

    Article  CAS  PubMed  Google Scholar 

  • Schlenk RF, Kayser S, Bullinger L et al (2014) Differential impact of allelic ratio and insertion site in FLT3-ITD-positive AML with respect to allogeneic transplantation. Blood 124(23):3441–3449

    Article  CAS  PubMed  Google Scholar 

  • Schlenk RF, Frech P, Weber D et al (2017) Impact of pretreatment characteristics and salvage strategy on outcome in patients with relapsed acute myeloid leukemia. Leukemia 31(5):1217–1220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schmaelter A-K, Labopin M, Socié G et al (2020) Inferior outcome of allogeneic stem cell transplantation for secondary acute myeloid leukemia in first complete remission as compared to de novo acute myeloid leukemia. Blood Cancer J 10(3):26–26

    Article  PubMed  PubMed Central  Google Scholar 

  • Schneider F, Hoster E, Unterhalt M et al (2012) The FLT3ITD mRNA level has a high prognostic impact in NPM1 mutated, but not in NPM1 unmutated, AML with a normal karyotype. Blood 119(19):4383–4386

    Article  CAS  PubMed  Google Scholar 

  • Schnittger S, Kinkelin U, Schoch C et al (2000) Screening for MLL tandem duplication in 387 unselected patients with AML identify a prognostically unfavorable subset of AML. Leukemia 14(5):796–804

    Article  CAS  PubMed  Google Scholar 

  • Schnittger S, Schoch C, Kern W et al (2005) Nucleophosmin gene mutations are predictors of favorable prognosis in acute myelogenous leukemia with a normal karyotype. Blood 106(12):3733–3739

    Article  CAS  PubMed  Google Scholar 

  • Schnittger S, Kohl TM, Haferlach T et al (2006) KIT-D816 mutations in AML1-ETO-positive AML are associated with impaired event-free and overall survival. Blood 107(5):1791–1799

    Article  CAS  PubMed  Google Scholar 

  • Schnittger S, Haferlach C, Ulke M, Alpermann T, Kern W, Haferlach T. IDH1 mutations are detected in 6.6% of 1414 AML patients and are associated with intermediate risk karyotype and unfavorable prognosis in adults younger than 60 years and unmutated NPM1 status. Blood. 2010;116(25):5486–96.

    Google Scholar 

  • Schnittger S, Bacher U, Kern W et al (2011a) Prognostic impact of FLT3-ITD load in NPM1 mutated acute myeloid leukemia. Leukemia 25(8):1297–1304

    Article  CAS  PubMed  Google Scholar 

  • Schnittger S, Dicker F, Kern W et al (2011b) RUNX1 mutations are frequent in de novo AML with noncomplex karyotype and confer an unfavorable prognosis. Blood 117(8):2348–2357

    Article  CAS  PubMed  Google Scholar 

  • Schnittger S, Eder C, Jeromin S et al (2013) ASXL1 exon 12 mutations are frequent in AML with intermediate risk karyotype and are independently associated with an adverse outcome. Leukemia 27(1):82–91

    Article  CAS  PubMed  Google Scholar 

  • Schoch C, Haferlach T, Haase D et al (2001) Patients with de novo acute myeloid leukaemia and complex karyotype aberrations show a poor prognosis despite intensive treatment: a study of 90 patients. Br J Haematol 112(1):118–126

    Article  CAS  PubMed  Google Scholar 

  • Schoch C, Schnittger S, Klaus M et al (2003) AML with 11q23/MLL abnormalities as defined by the WHO classification: incidence, partner chromosomes, FAB subtype, age distribution, and prognostic impact in an unselected series of 1897 cytogenetically analyzed AML cases. Blood 102(7):2395–2402

    Article  CAS  PubMed  Google Scholar 

  • Schoch C, Kern W, Schnittger S, Hiddemann W, Haferlach T (2004) Karyotype is an independent prognostic parameter in therapy-related acute myeloid leukemia (t-AML): an analysis of 93 patients with t-AML in comparison to 1091 patients with de novo AML. Leukemia 18(1):120–125

    Article  CAS  PubMed  Google Scholar 

  • Scholl S, Theuer C, Scheble V et al (2008) Clinical impact of nucleophosmin mutations and Flt3 internal tandem duplications in patients older than 60 yr with acute myeloid leukaemia. Eur J Haematol 80(3):208–215

    Article  CAS  PubMed  Google Scholar 

  • Schuurhuis GJ, Heuser M, Freeman S et al (2018) Minimal/measurable residual disease in AML: a consensus document from the European LeukemiaNet MRD working party. Blood 131(12):1275–1291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schwartz GW, Manning B, Zhou Y et al (2019) Classes of ITD predict outcomes in AML patients treated with FLT3 inhibitors. Clin Cancer Res 25(2):573–583

    Article  CAS  PubMed  Google Scholar 

  • Schwind S, Marcucci G, Maharry K et al (2010a) BAALC and ERG expression levels are associated with outcome and distinct gene and microRNA expression profiles in older patients with de novo cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. Blood 116(25):5660–5669

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schwind S, Maharry K, Radmacher MD et al (2010b) Prognostic significance of expression of a single microRNA, miR-181a, in cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. J Clin Oncol 28(36):5257–5264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seifert H, Mohr B, Thiede C et al (2009) The prognostic impact of 17p (p53) deletion in 2272 adults with acute myeloid leukemia. Leukemia 23(4):656–663

    Article  CAS  PubMed  Google Scholar 

  • Shen Y, Zhu Y-M, Fan X et al (2011) Gene mutation patterns and their prognostic impact in a cohort of 1185 patients with acute myeloid leukemia. Blood 118(20):5593–5603

    Article  CAS  PubMed  Google Scholar 

  • Shiah H-S, Kuo Y-Y, Tang J-L et al (2002) Clinical and biological implications of partial tandem duplication of the MLL gene in acute myeloid leukemia without chromosomal abnormalities at 11q23. Leukemia 16(2):196–202

    Article  CAS  PubMed  Google Scholar 

  • Shimada A, Iijima-Yamashita Y, Tawa A et al (2018) Risk-stratified therapy for children with FLT3-ITD-positive acute myeloid leukemia: results from the JPLSG AML-05 study. Int J Hematol 107(5):586–595

    Article  PubMed  Google Scholar 

  • Shin H-J, Min W-S, Min YH et al (2019) Different prognostic effects of core-binding factor positive AML with Korean AML registry data. Ann Hematol 98(5):1135–1147

    Article  CAS  PubMed  Google Scholar 

  • Silva P, Neumann M, Schroeder MP et al (2017) Acute myeloid leukemia in the elderly is characterized by a distinct genetic and epigenetic landscape. Leukemia 31(7):1640–1644

    Article  CAS  PubMed  Google Scholar 

  • Sitges M, Boluda B, Garrido A et al (2020) Scute myeloid leukemia with inv(3)(q21q26.2)/t(3;3)(q21;q26.2): study of 61 patients treated with intensive protocols. Eur J Haematol 105(2):138–147

    Article  CAS  PubMed  Google Scholar 

  • Slichter SJ (2004) Relationship between platelet count and bleeding risk in thrombocytopenic patients. Transfus Med Rev 18(3):153–167

    Article  PubMed  Google Scholar 

  • Slovak ML, Kopecky KJ, Cassileth PA et al (2000) Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. Blood 96(13):4075–4083

    Article  CAS  PubMed  Google Scholar 

  • Slovak ML, Gundacker H, Bloomfield CD et al (2006) A retrospective study of 69 patients with t(6;9)(p23;q34) AML emphasizes the need for a prospective, multicenter initiative for rare ‘poor prognosis’ myeloid malignancies. Leukemia 20(7):1295–1297

    Article  CAS  PubMed  Google Scholar 

  • Sorror ML, Maris MB, Storb R et al (2005) Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood 106(8):2912–2919

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sorror ML, Giralt S, Sandmaier BM et al (2007a) Hematopoietic cell transplantation–specific comorbidity index as an outcome predictor for patients with acute myeloid leukemia in first remission: combined FHCRC and MDACC experiences. Blood 110(13):4606–4613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sorror ML, Sandmaier BM, Storer BE et al (2007b) Comorbidity and disease status–based risk stratification of outcomes among patients with acute myeloid leukemia or myelodysplasia receiving allogeneic hematopoietic cell transplantation. J Clin Oncol 25(27):4246–4254

    Article  PubMed  Google Scholar 

  • Sorror ML, Storb RF, Sandmaier BM et al (2014) Comorbidity-age index: a clinical measure of biologic age before allogeneic hematopoietic cell transplantation. J Clin Oncol 32(29):3249–3256

    Article  PubMed  PubMed Central  Google Scholar 

  • Stengel A, Kern W, Haferlach T et al (2017) The impact of TP53 mutations and TP53 deletions on survival varies between AML, ALL, MDS and CLL: an analysis of 3307 cases. Leukemia 31(3):705–711

    Article  CAS  PubMed  Google Scholar 

  • Stengel A, Kern W, Meggendorfer M et al (2018) Number of RUNX1 mutations, wild-type allele loss and additional mutations impact on prognosis in adult RUNX1-mutated AML. Leukemia 32(2):295–302

    Article  CAS  PubMed  Google Scholar 

  • Stephens PJ, Greenman CD, Fu B et al (2011) Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell 144(1):27–40

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Steudel C, Wermke M, Schaich M et al (2003) Comparative analysis of MLL partial tandem duplication and FLT3 internal tandem duplication mutations in 956 adult patients with acute myeloid leukemia. Genes Chromosomes Cancer 37(3):237–251

    Article  CAS  PubMed  Google Scholar 

  • Stirewalt DL, Kopecky KJ, Meshinchi S et al (2001) FLT3, RAS, and TP53 mutations in elderly patients with acute myeloid leukemia. Blood 97(11):3589–3595

    Article  CAS  PubMed  Google Scholar 

  • Stirewalt DL, Kopecky KJ, Meshinchi S et al (2006) Size of FLT3 internal tandem duplication has prognostic significance in patients with acute myeloid leukemia. Blood 107(9):3724–3726

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stölzel F, Pfirrmann M, Aulitzky WE et al (2011) Risk stratification using a new prognostic score for patients with secondary acute myeloid leukemia: results of the prospective AML96 trial. Leukemia 25(3):420–428

    Article  PubMed  Google Scholar 

  • Stölzel F, Lüer T, Parmentier SB et al (2014) The prevalence of extramedullary AML detected by 18-FDG/PET-CT: results from the prospective PET-AML trial. Blood 124(21):2270–2270

    Article  Google Scholar 

  • Stölzel F, Mohr B, Kramer M et al (2016) Karyotype complexity and prognosis in acute myeloid leukemia. Blood Cancer J 6(1):e386

    Article  PubMed  PubMed Central  Google Scholar 

  • Straube J, Ling VY, Hill GR, Lane SW (2018) The impact of age, NPM1mut, and FLT3ITD allelic ratio in patients with acute myeloid leukemia. Blood 131(10):1148–1153

    Article  CAS  PubMed  Google Scholar 

  • Su L, Tan Y, Lin H et al (2018) Mutational spectrum of acute myeloid leukemia patients with double CEBPA mutations based on next-generation sequencing and its prognostic significance. Oncotarget 9(38):24970–24979

    Article  PubMed  PubMed Central  Google Scholar 

  • Su L, Gao S, Tan Y et al (2019) CSF3R mutations were associated with an unfavorable prognosis in patients with acute myeloid leukemia with CEBPA double mutations. Ann Hematol 98(7):1641–1646

    Article  CAS  PubMed  Google Scholar 

  • Suzuki T, Kiyoi H, Ozeki K et al (2005) Clinical characteristics and prognostic implications of NPM1 mutations in acute myeloid leukemia. Blood 106(8):2854–2861

    Article  CAS  PubMed  Google Scholar 

  • Tallman MS, Hakimian D, Shaw JM et al (1993) Granulocytic sarcoma is associated with the 8;21 translocation in acute myeloid leukemia. J Clin Oncol 11(4):690–697

    Article  CAS  PubMed  Google Scholar 

  • Tallman MS, Kim HT, Paietta E et al (2004) Acute monocytic leukemia (French-American-British classification M5) does not have a worse prognosis than other subtypes of acute myeloid leukemia: a report from the Eastern Cooperative Oncology Group. J Clin Oncol 22(7):1276–1286

    Article  PubMed  Google Scholar 

  • Tallman MS, Wang ES, Altman JK et al (2019) Acute myeloid Leukemia, version 3.2019, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw 17(6):721–749

    Article  CAS  Google Scholar 

  • Tang J-L, Hou H-A, Chen C-Y et al (2009) AML1/RUNX1 mutations in 470 adult patients with de novo acute myeloid leukemia: prognostic implication and interaction with other gene alterations. Blood 114(26):5352–5361

    Article  CAS  PubMed  Google Scholar 

  • Tarlock K, Alonzo TA, Moraleda PP et al (2014) Acute myeloid leukaemia (AML) with t(6;9)(p23;q34) is associated with poor outcome in childhood AML regardless of FLT3-ITD status: a report from the Children’s Oncology Group. Br J Haematol 166(2):254–259

    Article  PubMed  PubMed Central  Google Scholar 

  • Taskesen E, Bullinger L, Corbacioglu A et al (2011) Prognostic impact, concurrent genetic mutations, and gene expression features of AML with CEBPA mutations in a cohort of 1182 cytogenetically normal AML patients: further evidence for CEBPA double mutant AML as a distinctive disease entity. Blood 117(8):2469–2475

    Article  CAS  PubMed  Google Scholar 

  • Taub JW, Berman JN, Hitzler JK et al (2017) Improved outcomes for myeloid leukemia of Down syndrome: a report from the Children’s Oncology Group AAML0431 trial. Blood 129(25):3304–3313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • The Cancer Genome Atlas Research Network (2013) Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med 368(22):2059–2074

    Article  PubMed Central  CAS  Google Scholar 

  • Theis F, Corbacioglu A, Gaidzik VI et al (2016) Clinical impact of GATA2 mutations in acute myeloid leukemia patients harboring CEBPA mutations: a study of the AML study group. Leukemia 30(11):2248–2250

    Article  CAS  PubMed  Google Scholar 

  • Thiede C, Steudel C, Mohr B et al (2002) Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood 99(12):4326–4335

    Article  CAS  PubMed  Google Scholar 

  • Thiede C, Koch S, Creutzig E et al (2006) Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia (AML). Blood 107(10):4011–4020

    Article  CAS  PubMed  Google Scholar 

  • Thiede C, Bloomfield CD, Coco FL et al (2007) The high prevalence of FLT3-ITD mutations is associated with the poor outcome in adult patients with t(6;9)(p23;q34) positive AML—results of an international metaanalysis. Blood 110(11):761–761

    Article  Google Scholar 

  • Thol F, Damm F, Wagner K et al (2010) Prognostic impact of IDH2 mutations in cytogenetically normal acute myeloid leukemia. Blood 116(4):614–616

    Article  CAS  PubMed  Google Scholar 

  • Thol F, Damm F, Lüdeking A et al (2011) Incidence and prognostic influence of DNMT3A mutations in acute myeloid leukemia. J Clin Oncol 29(21):2889–2896

    Article  CAS  PubMed  Google Scholar 

  • Thol F, Kölking B, Hollink IHI et al (2013) Analysis of NUP98/NSD1 translocations in adult AML and MDS patients. Leukemia 27(3):750–754

    Article  CAS  PubMed  Google Scholar 

  • Tien F-M, Hou H-A, Tsai C-H et al (2018a) Hyperleukocytosis is associated with distinct genetic alterations and is an independent poor-risk factor in de novo acute myeloid leukemia patients. Eur J Haematol 101(1):86–94

    Article  CAS  PubMed  Google Scholar 

  • Tien F-M, Hou H-A, Tang J-L et al (2018b) Concomitant WT1 mutations predict poor prognosis in acute myeloid leukemia patients with double mutant CEBPA. Haematologica 103(11):e510–e513

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Torrebadell M, Díaz-Beyá M, Kalko SG et al (2018) A 4-gene expression prognostic signature might guide post-remission therapy in patients with intermediate-risk cytogenetic acute myeloid leukemia. Leuk Lymphoma 59(10):2394–2404

    Article  CAS  PubMed  Google Scholar 

  • Touw IP, Sanders MA (2020) Mutant allelic burden in acute myeloid leukaemia: why bother? Br J Haematol 188(6):817–818

    Article  PubMed  Google Scholar 

  • Tsai C-H, Hou H-A, Tang J-L et al (2016) Genetic alterations and their clinical implications in older patients with acute myeloid leukemia. Leukemia 30(7):1485–1492

    Article  CAS  PubMed  Google Scholar 

  • Tsimberidou A-M, Kantarjian HM, Wen S et al (2008) Myeloid sarcoma is associated with superior event-free survival and overall survival compared with acute myeloid leukemia. Cancer 113(6):1370–1378

    Article  PubMed  Google Scholar 

  • Tsuji K, Motoji T, Sugawara I et al (2000) Significance of lung resistance-related protein in the clinical outcome of acute leukaemic patients with reference to P-glycoprotein. Br J Haematol 110(2):370–378

    Article  CAS  PubMed  Google Scholar 

  • Valk PJM, Verhaak RGW, Beijen MA et al (2004) Prognostically useful gene-expression profiles in acute myeloid leukemia. N Engl J Med 350:1617–1628. https://doi.org/10.1056/NEJMoa040465

    Article  CAS  PubMed  Google Scholar 

  • van Solinge TS, Zeijlemaker W, Ossenkoppele GJ, Cloos J, Schuurhuis GJ (2018) The interference of genetic associations in establishing the prognostic value of the immunophenotype in acute myeloid leukemia. Cytometry B Clin Cytom 94(1):151–158

    Article  PubMed  CAS  Google Scholar 

  • Vasu S, Kohlschmidt J, Mrózek K et al (2018) Ten-year outcome of patients with acute myeloid leukemia not treated with allogeneic transplantation in first complete remission. Blood Adv 2(13):1645–1650

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Venditti A, Poeta GD, Maurillo L et al (2004) Combined analysis of bcl-2 and MDR1 proteins in 256 cases of acute myeloid leukemia. Haematologica 89(8):934–939

    CAS  PubMed  Google Scholar 

  • Verhaak RGW, Goudswaard CS, van Putten W et al (2005) Mutations in nucleophosmin (NPM1) in acute myeloid leukemia (AML): association with other gene abnormalities and previously established gene expression signatures and their favorable prognostic significance. Blood 106(12):3747–3754

    Article  CAS  PubMed  Google Scholar 

  • Versluis J, Hout FEM (2017) In ‘t, Devillier R, et al. Comparative value of post-remission treatment in cytogenetically normal AML subclassified by NPM1 and FLT3 -ITD allelic ratio. Leukemia 31(1):26–33

    Article  CAS  PubMed  Google Scholar 

  • Vetro C, Haferlach T, Meggendorfer M et al (2020) Cytogenetic and molecular genetic characterization of KMT2A-PTD positive acute myeloid leukemia in comparison to KMT2A-rearranged acute myeloid leukemia. Cancer Genet 240:15–22

    Article  CAS  PubMed  Google Scholar 

  • Virappane P, Gale R, Hills R et al (2008) Mutation of the Wilms’ tumor 1 gene is a poor prognostic factor associated with chemotherapy resistance in normal karyotype acute myeloid leukemia: the United Kingdom Medical Research Council Adult Leukaemia Working Party. J Clin Oncol 26(33):5429–5435

    Article  CAS  PubMed  Google Scholar 

  • von Neuhoff C, Reinhardt D, Sander A et al (2010) Prognostic impact of specific chromosomal aberrations in a large group of pediatric patients with acute myeloid leukemia treated uniformly according to trial AML-BFM 98. J Clin Oncol 28(16):2682–2689

    Article  CAS  Google Scholar 

  • Wagner K, Damm F, Göhring G et al (2010) Impact of IDH1 R132 mutations and an IDH1 single nucleotide polymorphism in cytogenetically normal acute myeloid leukemia: SNP rs11554137 is an adverse prognostic factor. J Clin Oncol 28(14):2356–2364

    Article  CAS  PubMed  Google Scholar 

  • Wakita S, Yamaguchi H, Ueki T et al (2016) Complex molecular genetic abnormalities involving three or more genetic mutations are important prognostic factors for acute myeloid leukemia. Leukemia 30(3):545–554

    Article  CAS  PubMed  Google Scholar 

  • Walker CJ, Kohlschmidt J, Eisfeld A-K et al (2019) Genetic characterization and prognostic relevance of acquired uniparental disomies in cytogenetically normal acute myeloid leukemia. Clin Cancer Res 25(21):6524–6531

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang B, Liu Y, Hou G et al (2016) Mutational spectrum and risk stratification of intermediate-risk acute myeloid leukemia patients based on next-generation sequencing. Oncotarget 7(22):32065–32078

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang M, Lindberg J, Klevebring D et al (2017) Validation of risk stratification models in acute myeloid leukemia using sequencing-based molecular profiling. Leukemia 31(10):2029–2036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wattad M, Weber D, Döhner K et al (2017) Impact of salvage regimens on response and overall survival in acute myeloid leukemia with induction failure. Leukemia 31(6):1306–1313

    Article  CAS  PubMed  Google Scholar 

  • Weber S, Alpermann T, Dicker F et al (2014) BAALC expression: a suitable marker for prognostic risk stratification and detection of residual disease in cytogenetically normal acute myeloid leukemia. Blood Cancer J 4(1):e173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weber S, Haferlach T, Haferlach C, Kern W (2016) Comprehensive study on ERG gene expression in normal karyotype acute myeloid leukemia: ERG expression is of limited prognostic value, whereas the accumulation of adverse prognostic markers stepwise worsens the prognosis. Blood Cancer J 6(12):e507

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weinberg OK, Ohgami RS, Ma L et al (2014) Acute myeloid leukemia with monosomal karyotype: morphologic, immunophenotypic, and molecular findings. Am J Clin Pathol 142(2):190–195

    Article  PubMed  Google Scholar 

  • Weinberg OK, Gibson CJ, Blonquist TM et al (2017) NPM1 mutation but not RUNX1 mutation or multilineage dysplasia defines a prognostic subgroup within de novo acute myeloid leukemia lacking recurrent cytogenetic abnormalities in the revised 2016 WHO classification. Am J Hematol 92(7):E123–E124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weissmann S, Alpermann T, Grossmann V et al (2012) Landscape of TET2 mutations in acute myeloid leukemia. Leukemia 26(5):934–942

    Article  CAS  PubMed  Google Scholar 

  • Whitman SP, Archer KJ, Feng L et al (2001) Absence of the wild-type allele predicts poor prognosis in adult de novo acute myeloid leukemia with normal cytogenetics and the internal tandem duplication of FLT3: a Cancer and Leukemia Group B study. Cancer Res 61(19):7233–7239

    CAS  PubMed  Google Scholar 

  • Whitman SP, Maharry K, Radmacher MD et al (2010) FLT3 internal tandem duplication associates with adverse outcome and gene- and microRNA-expression signatures in patients 60 years of age or older with primary cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. Blood 116(18):3622–3626

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wierzbowska A, Wawrzyniak E, Siemieniuk-Rys M et al (2017) Concomitance of monosomal karyotype with at least 5 chromosomal abnormalities is associated with dismal treatment outcome of AML patients with complex karyotype—retrospective analysis of Polish Adult Leukemia Group (PALG). Leuk Lymphoma 58(4):889–897

    Article  PubMed  Google Scholar 

  • Wiggers CRM, Baak ML, Sonneveld E et al (2019) AML subtype is a major determinant of the association between prognostic gene expression signatures and their clinical significance. Cell Rep 28(11):2866–2877.e5

    Article  CAS  PubMed  Google Scholar 

  • Wilhelmson AS, Porse BT (2020) CCAAT enhancer binding protein alpha (CEBPA) biallelic acute myeloid leukaemia: cooperating lesions, molecular mechanisms and clinical relevance. Br J Haematol 190(4):495–507

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wouters BJ, Löwenberg B, Erpelinck-Verschueren CAJ et al (2009) Double CEBPA mutations, but not single CEBPA mutations, define a subgroup of acute myeloid leukemia with a distinctive gene expression profile that is uniquely associated with a favorable outcome. Blood 113(13):3088–3091

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu X, Feng X, Zhao X et al (2016) Prognostic significance of FLT3-ITD in pediatric acute myeloid leukemia: a meta-analysis of cohort studies. Mol Cell Biochem 420(1–2):121–128

    Article  CAS  PubMed  Google Scholar 

  • Xu Q, Li Y, Lv N et al (2017) Correlation between isocitrate dehydrogenase gene aberrations and prognosis of patients with acute myeloid leukemia: a systematic review and meta-analysis. Clin Cancer Res 23(15):4511–4522

    Article  CAS  PubMed  Google Scholar 

  • Yamato G, Shiba N, Yoshida K et al (2018) RUNX1 mutations in pediatric acute myeloid leukemia are associated with distinct genetic features and an inferior prognosis. Blood 131(20):2266–2270

    Article  CAS  PubMed  Google Scholar 

  • Yanada M, Yamamoto Y, Iba S et al (2016) TP53 mutations in older adults with acute myeloid leukemia. Int J Hematol 103(4):429–435

    Article  CAS  PubMed  Google Scholar 

  • Yang X, Wong MPM, Ng RK (2019) Aberrant DNA methylation in acute myeloid leukemia and its clinical implications. Int J Mol Sci 20(18):4576

    Article  CAS  PubMed Central  Google Scholar 

  • Yoshizato T, Nannya Y, Atsuta Y et al (2017) Genetic abnormalities in myelodysplasia and secondary acute myeloid leukemia: impact on outcome of stem cell transplantation. Blood 129(17):2347–2358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yuan X-Q, Chen P, Du Y-X et al (2019) Influence of DNMT3A R882 mutations on AML prognosis determined by the allele ratio in Chinese patients. J Transl Med 17(1):220

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang Y, Wang F, Chen X et al (2019) Companion gene mutations and their clinical significance in AML with double mutant CEBPA. Cancer Gene Ther 27(7-8):599–606

    Article  PubMed  CAS  Google Scholar 

  • Zhou J, Zhang T, Xu Z et al (2019a) BCL2 overexpression: clinical implication and biological insights in acute myeloid leukemia. Diagn Pathol 14:68

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhou F, Zhou F, Du M et al (2019b) Comprehensive prognostic scoring systems could improve the prognosis of adult acute myeloid leukemia patients. Int J Hematol 110(5):575–583

    Article  CAS  PubMed  Google Scholar 

  • Zhou W, Chen G, Gong D et al (2020) Loss of the Y chromosome predicts a high relapse risk in younger adult male patients with t(8;21) acute myeloid leukemia on high-dose cytarabine consolidation therapy: a retrospective multicenter study. Leuk Lymphoma 61(4):820–830

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Raphael Itzykson .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Itzykson, R., Cerrano, M., Esteve, J. (2021). Prognostic Factors in AML. In: Röllig, C., Ossenkoppele, G.J. (eds) Acute Myeloid Leukemia . Hematologic Malignancies. Springer, Cham. https://doi.org/10.1007/978-3-030-72676-8_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-72676-8_7

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-72675-1

  • Online ISBN: 978-3-030-72676-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics