BCR-ABL as a target for novel therapeutic interventions

Expert Opin Ther Targets. 2002 Feb;6(1):85-101. doi: 10.1517/14728222.6.1.85.

Abstract

The BCR-ABL oncogene is the result of a reciprocal translocation between the long arms of chromosome 9 and 22 t(9; 22). There is good experimental evidence demonstrating that BCR-ABL is the single causative abnormality in chronic myeloid leukaemia (CML), making it a unique model for the development of molecular targets. In addition to CML, BCR-ABL transcripts can be found in a minority of acute lymphoblastic leukaemias and very rarely in acute myeloid leukaemia (AML). Elucidating the molecular mechanisms and downstream pathways of BCR-ABL has led to the design of several novel therapeutic approaches. In this review, molecular targeting of BCR-ABL will be discussed based on the inhibition of protein tyrosine kinase activity, antisense strategies and immunomodulation.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Transformation, Neoplastic / drug effects
  • Fusion Proteins, bcr-abl
  • Genes, abl / drug effects
  • Genes, abl / genetics*
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Protein-Tyrosine Kinases / drug effects*
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism
  • Signal Transduction / drug effects
  • T-Lymphocytes / drug effects

Substances

  • Antineoplastic Agents
  • Protein-Tyrosine Kinases
  • Fusion Proteins, bcr-abl