Molecular biology of chronic myeloid leukemia

Int J Hematol. 2001 Apr;73(3):308-22. doi: 10.1007/BF02981955.

Abstract

Multistep carcinogenesis is exemplified by chronic myeloid leukemia with clinical manifestation consisting of a chronic phase and blast crisis. Pathological generation of BCR-ABL (breakpoint cluster region-Abelson) results in growth promotion, differentiation, resistance to apoptosis, and defect in DNA repair in targeted blood cells. Domains in BCR and ABL sequences work in concert to elicit a variety of leukemogenic signals including Ras, STAT5 (signal transducer and activator of transcription-5), Myc, cyclin D1, P13 (phosphatidylinositol 3-kinase), RIN1 (Ras interaction/interference), and activation of actin cytoskeleton. However, the mechanism of differentiation of transformed cells is poorly understood. A mutator phenotype of BCR-ABL could explain the transformation to blast crisis. The aim of this review is to integrate molecular and biological information on BCR, ABL, and BCR-ABL and to focus on how signaling from those molecules mirrors the biological phenotypes of chronic myeloid leukemia.

Publication types

  • Review

MeSH terms

  • Animals
  • Blast Crisis / genetics
  • Cell Differentiation
  • Cell Transformation, Neoplastic / genetics
  • Disease Progression
  • Fusion Proteins, bcr-abl / chemistry
  • Fusion Proteins, bcr-abl / genetics*
  • Fusion Proteins, bcr-abl / physiology
  • Gene Expression Regulation, Leukemic
  • Genes, abl
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / enzymology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Leukemia, Myeloid, Accelerated Phase / genetics
  • Leukemia, Myeloid, Chronic-Phase / genetics
  • Mice
  • Mice, Knockout
  • Models, Biological
  • Neoplasm Proteins / physiology
  • Neoplastic Stem Cells / enzymology
  • Neoplastic Stem Cells / pathology
  • Oncogene Proteins / chemistry
  • Oncogene Proteins / genetics
  • Oncogene Proteins / physiology
  • Phenotype
  • Philadelphia Chromosome
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary
  • Protein-Tyrosine Kinases*
  • Proto-Oncogene Proteins c-abl / chemistry
  • Proto-Oncogene Proteins c-abl / genetics
  • Proto-Oncogene Proteins c-abl / physiology
  • Proto-Oncogene Proteins c-bcr
  • Proto-Oncogene Proteins*
  • Rats
  • Signal Transduction
  • Structure-Activity Relationship

Substances

  • Neoplasm Proteins
  • Oncogene Proteins
  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases
  • Fusion Proteins, bcr-abl
  • Proto-Oncogene Proteins c-abl
  • BCR protein, human
  • Bcr protein, mouse
  • Proto-Oncogene Proteins c-bcr