Skip to main content
SpringerLink
Log in

Genetic Approaches to Defining Signaling by the CML-Associated Tyrosine kinase BCR-ABL1

  • Conference paper
Gene Technology

Part of the book series: NATO ASI Series ((ASIH,volume 94))

  • 130 Accesses

Abstract

Human chronic myelogenous leukemia (CML) is a cancer that is associated with a specific cytogenetic marker known as the Philadelphia (Ph1) chromosome (Nowell and Hungerford, 1960; Rowley, 1973; reviewed in Kurzrock et al. , 1988). Cells of multiple lineages carry Ph1, suggesting that the disease originates in a pluripotent stem cell. Ph1 is the result of a reciprocal translocation of chromosomes 9 and 22, which results in the fusion of two cellular genes encoding BCR and c-ABL (Shtivelman et al. , 1985; Clark et al. , 1988). The resulting fusion gene (see Figure 1) encodes BCR-ABL, an activated protein tyrosine kinase. The tyrosine kinase activity of BCR-ABL is deregulated when compared to c-ABL (Konopka and Witte, 1985) and is the most essential feature for its transforming activity. In nature two fusion products are detected. P210 BCR-ABL is associated with CML and P185 BCR-ABL is associated with the more aggressive acute lymphocytic leukemia (ALL). The tyrosine kinase activity of P185 is more potent than P210 kinase activity, which also correlates with their respective transforming activities (Lugo et al. , 1990).

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight 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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Afar, D.E.H., A. Goga, J. McLaughlin, O. Witte, and C.L. Sawyers. 1994.Differential rescue of Bcr-Abl point mutants with c-Myc. Science 264:424–426

    Article  PubMed  CAS  Google Scholar 

  • Ayer, D.E., L. Kretzner, and R.N. Eisenman. 1993.Mad: A heterodimeric partner for max that antagonizes Myc transcriptional activity. Cell 72:211–222

    Article  PubMed  CAS  Google Scholar 

  • Blackwood, E.M., and R.N. Eisenman. 1991.Max: A helix-loophelix zipper protein that forms a sequence-specific DNAbinding complex with myc. Science 251:1211–1213

    Article  PubMed  CAS  Google Scholar 

  • Boguski, M., and F. McCormick.1993.Proteins regulating Ras and its relatives. Nature 366:643–654

    Article  PubMed  CAS  Google Scholar 

  • Clark, S.C., J. McLaughlin, M. Timmons, A.M. Pendergast, Y. Ben-Neriah, L.W. Dow, W. Crist, G. Rovera, S.D. Smith, and O.N. Witte. 1988.Expression of a distinctive BCR-ABL oncogene in Phi-positive acute lymphocytic leukemia (ALL). Science 239:775–777

    Article  PubMed  CAS  Google Scholar 

  • Cohen, L., R. Mohr, Y.-Y. Chen, M. Huang, R. Kato, D. Dorin, F. Tamanoi, A. Goga, D. Afar, N. Rosenberg, and O. Witte. 1994.Transcriptional activation of a novel ras-like gene (kir) by oncogenic tyrosine kinases. Proc. Natl. Acad. Sci. USA 91:12448–12452

    Article  PubMed  CAS  Google Scholar 

  • Daley, G.Q., R.A. Van Etten, and D. Baltimore. 1990.Induction of chronic myelogenous leukemia in mice by the ?210bcr/abl gene of the Philadelphia chromosome. Science 247:824–830

    Article  PubMed  CAS  Google Scholar 

  • Dang, C.V., M. McGuire, M. Buckmire, and W.M.F. Lee.1989.Involvement of the ’leucine zipper’ region in the oligomerization and transforming activity of human c-myc protein. Nature 337:664–666

    Article  PubMed  CAS  Google Scholar 

  • DeClue, J.E., K. Zhang, P. Redford, W.C. Vass, and D.R. Lowy. 1991.Suppression of src transformation by overexpression of full-length GTPase-activating protein (GAP) or of the GAPC terminus. Mol. Cell. Biol. 11:2819–2825

    PubMed  CAS  Google Scholar 

  • Diekmann, D., S. Brill, M.D. Garrett, N. Totty, J. Hsuan, C. Monfries, C. Hall, L. Lim, and A. Hall. 1991. Bcr encodes a GTPase activating protein for p21rflc. Nature 351:400–402

    Article  PubMed  CAS  Google Scholar 

  • Elefanty, A.G., I.K. Hariharan, and S. Cory, 1990. Bcr-abl the hallmark of chronic myeloid leukaemia in man, induces multiple haemopoietic neoplasms in mice. EMBO J. 9:1069–1078

    PubMed  CAS  Google Scholar 

  • Feig, L.A., and G.M. Cooper. 1988.Inhibition of NIH 3T3 cell proliferation by a mutant ras protein with preferential affinity for GDP. Mol. Cell. Biol. 8:3235–3243

    PubMed  CAS  Google Scholar 

  • Gishizky, M.L., J. Johnson-White, and O.N. Witte. 1993.Efficient transplantation of BCR/ABL induced CML like syndrome in mice. Proc. Natl. Acad. Sci. USA 90:3755–3759

    Article  PubMed  CAS  Google Scholar 

  • Goga, A., J. McLaughlin, A.M. Pendergast, K. Parmar, A. Muller, N. Rosenberg, and O.N. Witte. 1993.Oncogenic activation of c-ABL by mutation within its last exon. Mol. Cell. Biol. 13:4967–4975

    PubMed  CAS  Google Scholar 

  • Heisterkamp, N., G. Jenster, J. ten Hoeve, D. Zovich, P.K. Pattengale, and J. Groffen.1990.Acute leukaemia in bcr/abl transgenic mice. Nature 344:251–253

    Article  PubMed  CAS  Google Scholar 

  • Kantarijan, H.M., A. Deisseroth, R. Kurzrock, Z. Estrov, and M. Talpaz. 1993.Chronic myelogenous leukemia: a concise update. Blood 82:691–703

    Google Scholar 

  • Kato, G.J., J. Barrett, M. Villa-Garcia, and C.V. Dang. 1990.An amino-terminal c-Myc domain required for neoplastic transformation activates transcription. Mol. Cell. Biol. 10:5914–5920

    PubMed  CAS  Google Scholar 

  • Kelliher, M., A. Knott, J. McLaughlin, O.N. Witte, and N. Rosenberg. 1991.Differences in Oncogenic Potency but Not Target Cell Specificity Distinguish the Two Forms of the BCR/ABL Oncogene. Mol. Cell. Biol. 11:4710–4716

    PubMed  CAS  Google Scholar 

  • Kelliher, M.A., J. McLaughlin, O.N. Witte, and N. Rosenberg. 1990.Induction of a chronic myelogenous leukemia-like syndrome in mice with v-aJbl and BCR/ABL. Proc. Natl. Acad. Sci. USA 87:6649–6653

    Article  PubMed  CAS  Google Scholar 

  • Kipreos, E.T., and J.Y.J. Wang. 1992.Cell cycle-regulated binding of c-Abl tyrosine kinase to DNA. Science 256:382–385

    Article  PubMed  CAS  Google Scholar 

  • Koch, C.A., D. Anderson, M.F. Moran, C. Ellis, and T. Pawson. 1991.SH2 and SH3 Domains: Elements That Control Interactions of Cytoplasmic Signaling Proteins. Science 252:668–674

    Article  PubMed  CAS  Google Scholar 

  • Konopka, J.B., and O.N. Witte. 1985.Detection of cabl tyrosine kinase activity in vitro permits direct comparison of normal and altered abl gene products. Mol. Cell. Biol. 5:3116–3123

    PubMed  CAS  Google Scholar 

  • Kurzrock, R., J.U. Gutterman, and M. Talpaz. 1988.The molecular genetics of Philadelphia chromosome-positive leukemias. N. Engl. J. Med. 319:990–998

    Article  PubMed  CAS  Google Scholar 

  • Liang, P., and A.B. Pardee.1992.Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction. Science 257:967–971

    Article  PubMed  CAS  Google Scholar 

  • Lugo, T., and O.N. Witte. 1989.The BCR/ABL oncogene transforms Rat-1 cells and cooperates with v-myc. Mol. Cell. Biol. 9:1263–1270

    PubMed  CAS  Google Scholar 

  • Lugo, T.G., A. Pendergast, A.J. Muller, and O.N. Witte. 1990.Tyrosine kinase activity and transformation potency of bcr-abl oncogene products. Science 247:1079–1082

    Article  PubMed  CAS  Google Scholar 

  • Maru, Y.M., and O.N. Witte.1991. The BCR gene encodes a novel serine/threonine kinase activity within a single exon. Cell 67:459–468

    Article  PubMed  CAS  Google Scholar 

  • McLaughlin, J., E. Chianese, and O.N. Witte. 1987.In vitro transformation of immature hematopoietic cells by the P210 BCR/ABL oncogene product of the Philadelphia chromosome. Proc. Natl. Acad. Sci. USA 84:6558–6562

    Article  PubMed  CAS  Google Scholar 

  • McWhirter, J.R., and J.Y.J. Wang. 1991.Activation of Tyrosine Kinase and Microfilament-Binding Functions of c-abl by bcr Sequences in bcr/abl Fusion Proteins. Mol. Cell. Biol. 11:1553–1565

    PubMed  CAS  Google Scholar 

  • Nowell, P.C., and D.A. Hungerford. 1960.A minute chromosome in human chronic granulocytic leukemia. Science 132:p.1497

    Google Scholar 

  • Pawson, T., and G.D. Gish. 1992.SH2 and SH3 Domains: from structure to function. Cell 71:359–362

    Article  PubMed  CAS  Google Scholar 

  • Pendergast, A.M., M.L. Gishizky, M.H. Havlik, and O.N. Witte. 1993a.SHI domain autophosphorylation of P210 BCR/ABL is required for transformation but not growth factorindependence. Mol. Cell. Biol. 13:1728–1736

    PubMed  CAS  Google Scholar 

  • Pendergast, A.M., L.A. Quilliam, L.D. Cripe, C.H. Bassing, Z. Dai, N. Li, A. Batzer, K.M. Rabun, C.J. Der, J. Schlessinger, and M.L. Gishizky. 1993b.BCR-ABL-induced oncogenesis is mediated by direct interaction with the SH2 domain of the GRB-2 adaptor protein. Cell 75:175–185

    PubMed  CAS  Google Scholar 

  • Prendergast, G.C., D. Lawe, and E.B. Ziff. 1991.Association of Myn, the Murine Homolog of Max, with c-Myc Stimulates Methylation-Sensitive DNA Binding and Ras Cotransformation. Cell 65:395–407

    Article  PubMed  CAS  Google Scholar 

  • Reynet, C., and C.R. Kahn. 1993.Rad: A Member of the Ras Family Overexpressed in Muscle of Type II Diabetic Humans. Science 262:1441–1444

    Article  PubMed  CAS  Google Scholar 

  • Ron, D., M. Zannini, M. Levis, R.B. Wickner, L.T. Hunt, G. Graziani, S.R. Tronick, S.A. Aaronson, and A. Eva. 1991.A region of proto-dbl essential for its transforming activity shows sequence similarity to a yeast cell cycle gene, CDC 24, and the human breakpoint cluster gene, bcr. New Biolog. 3:372–379

    CAS  Google Scholar 

  • Rosenberg,N., and O.N. Witte. 1988.The viral and cellular forms of the Abelson (abl) oncogene. Adv. in Virus Res. 39:39–81

    Article  Google Scholar 

  • Rowley, J.D. 1973. A new consistent chromosomal abnormality in chronic myelogenous leukemia identified by quinacrine fluorescence and giemsa staining. Nature 243:290–293

    Article  PubMed  CAS  Google Scholar 

  • Sawyers, C.L., W. Callahan, and O.N. Witte. 1992.Dominant negative myc blocks transformation by ABL oncogenes. Cell 70:901–910

    Article  PubMed  CAS  Google Scholar 

  • Sawyers, C.L., J. McLaughlin, A. Goga, M. Havlik, and O. Witte. 1994.The nuclear tyrosine kinase c-Abl negatively regulates cell growth. Cell 77:121–131

    Article  PubMed  CAS  Google Scholar 

  • Scott, M.L., R.A. Van Etten, G.Q. Daley, and D. Baltimore. 1991. v-aJbl causes hematopoietic disease distinct from that caused by bcr-abl. Proc. Natl. Acad. Sci. USA 88:6506–6510

    Article  PubMed  CAS  Google Scholar 

  • Shtivelman, E., B. Lifshitz, R.P. Gale, and E. Canaani. 1985.Fused transcript of abl and bcr genes in chronic myelogenous leukaemia. Nature 315:550–554

    Article  PubMed  CAS  Google Scholar 

  • Stacey, D.W., L.A. Feig, and J.B. Gibbs. 1991a.Dominant inhibitory Ras mutants selectively inhibit the activity of either cellular or oncogenic Ras. Mol. Cell. Biol. 11:4053–4064

    PubMed  CAS  Google Scholar 

  • Stacey, D.W., M. Roudebush, R. Day, S.D. Mosser, J.B. Gibbs, and L.A. Feig. 1991b. Dominant inhibitory Ras mutants demonstrate the requirement for Ras activity in the action of tyrosine kinase oncogenes. Oncogene 6:2297–23 04

    PubMed  CAS  Google Scholar 

  • Thomas, S.M., M. DeMarco, G. D’Arcangelo, S. Halegoua, and J.S. Brugge. 1992.Ras is essential for nerve growth factor- and phorbol ester-induced tyrosine phosphorylation of MAP kinases. Cell 68:1031–1040

    Article  PubMed  CAS  Google Scholar 

  • Van Etten, R.A., P. Jackson, and D. Baltimore. 1989.The mouse type IV c-aJbl gene product is a nuclear protein, and activation of transforming ability is associated withcytoplasmic localization. Cell 58:669–678

    Article  PubMed  Google Scholar 

  • Waksman, G., D. Kominos, S.C. Robertson, N. Pant, D. Baltimore, R.B. Birge, D. Cowburn, H. Hanafusa, B.J. Mayer, M. Overduin, M.D. Resh, C.B. Rios, L. Silverman, and J. Kuriyan. 1992.Crystal structure of the phosphotyrosine recognition domain SH2 of v-src complexed with tyrosine-phosphorylated peptides. Nature 358:646–653

    Article  PubMed  CAS  Google Scholar 

  • Welch, P.J.,and J.Y.J. Wang. 1993. AC-terminal proteinbinding domain in the retinoblastoma protein regulates nuclear c-Abl tyrosine kinase in the cell cycle. Cell 75:779–790

    Article  PubMed  CAS  Google Scholar 

  • Wood, K.W., C. Sarnecki, T.M. Roberts, and J. Blenis. 1992.Ras mediates nerve growth factor receptor modulation of three signal-transducing protein kinases: Map kinase, Raf-1 and RSK. Cell 68:1041–1050

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Microbiology and Molecular Genetics Molecular, Biology Institute and Howard Hughes Medical Institute University of California-Los Angeles, 5-748 MacDonald Building 10833 Le Conte Ave, Los Angeles, CA, 90024-1662, USA

    Daniel E. H. Afar, Andrei Goga, Lucie Cohen, Charles L. Sawyers, Jami McLaughlin, Randolph N. Mohr & Owen N. Witte

Authors
  1. Daniel E. H. Afar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andrei Goga
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lucie Cohen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Charles L. Sawyers
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jami McLaughlin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Randolph N. Mohr
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Owen N. Witte
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Universitätskrankenhaus Eppendorf, Martinistraße 52, D-20246, Hamburg, Germany

    Axel R. Zander

  2. Heinrich-Pette-lnstitut für Experimentelle Virologie und Immunologie, Universität Hamburg, Martinistraße 52, D-20246, Hamburg, Germany

    Wolfram Ostertag

  3. City Center for Advanced Medical Technologies, Bone Marrow Transplantation Center, Pr. Dynamo 3, 197042, St.Petersburg, Russia

    Boris V. Afanasiev

  4. Laboratory for Gene Structure Expression, Medical Research Council Institute, The Ridgeway, Mill Hill, London, NW71AA, UK

    Frank Grosveld

Rights and permissions

Reprints and permissions

Copyright information

© 1996 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Afar, D.E.H. et al. (1996). Genetic Approaches to Defining Signaling by the CML-Associated Tyrosine kinase BCR-ABL1. In: Zander, A.R., Ostertag, W., Afanasiev, B.V., Grosveld, F. (eds) Gene Technology. NATO ASI Series, vol 94. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-61122-3_18

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-61122-3_18

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-64704-8

  • Online ISBN: 978-3-642-61122-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation