4. Molecular Pathogenesis of BCR-ABL in Chronic Myeloid Leukemia

  1. Hussain I. Saba MD, PHD2 and
  2. Ghulam J. Mufti MB, DM, FRCP, FRCPATH3
  1. Eric Padron,
  2. Lori A. Hazlehurst and
  3. Javier Pinilla-Ibarz

Published Online: 24 MAR 2011

DOI: 10.1002/9781444394016.ch4

Advances in Malignant Hematology

Advances in Malignant Hematology

How to Cite

Padron, E., Hazlehurst, L. A. and Pinilla-Ibarz, J. (2011) Molecular Pathogenesis of BCR-ABL in Chronic Myeloid Leukemia, in Advances in Malignant Hematology (eds H. I. Saba and G. J. Mufti), Wiley-Blackwell, Oxford, UK. doi: 10.1002/9781444394016.ch4

Editor Information

  1. 2

    James A. Haley Veterans' Hospital, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida College of Medicine, Tampa, FL, USA

  2. 3

    Department of Haematological Medicine, Guy's and St Thomas' School of Medicine, King's College Hospital, London, UK

Author Information

  1. Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA

Publication History

  1. Published Online: 24 MAR 2011
  2. Published Print: 16 APR 2011

ISBN Information

Print ISBN: 9781405196260

Online ISBN: 9781444394016

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Keywords:

  • chronic myeloid leukemia;
  • CML;
  • BCR-ABL;
  • imatinib;
  • stem cell;
  • hedgehog;
  • Wnt1;
  • STAT;
  • acute lymphoblastic leukemia;
  • ALL;
  • chronic neutrophilic leukemia;
  • CNL

Summary

The BCR-ABL translocation represents the first pathognomonic genetic event described in oncology. It is now known that a reciprocal translocation results in a fusion of the breakpoint cluster region (BCR) gene on chromosome 22 and the c-Abl gene on chromosome 9. This fusion kinase (BCR-ABL) provides antiapoptotic and proliferative signals that confer a competitive Darwinian advantage to the malignant clone. The advent of imatinib, a BCR-ABL tyrosine kinase inhibitor, first provided proof-of-principle that molecularly targeted therapy could be an effective, non-toxic treatment for many cancers. Here, we discuss the molecular pathology of BCR-ABL in CML as it relates to oncogenesis, therapy, and drug resistance.