The molecular biology of chronic myeloid leukaemia

Leukemia. 1996 May;10(5):751-6.


Chronic myeloid leukaemia (CML) is characterized cytogenetically by a t(9;22)(q34;ql1) reciprocal translocation which gives origin to a hybrid BCR-ABL gene, encoding a p2lO(BCR-ABL) fusion protein with elevated tyrosine kinase activity and transforming abilities. The t(9;22) was suggested to be associated with genomic imprinting of centromeric regions of chromosomes 9 and 22, but the genes directly affected by the translocation, ABL and BCR, were shown not to be imprinted. For most diagnostic and research purposes the BCR-ABL gene can be efficiently identified by reverse-transcription and polymerase chain reaction (RT/PCR) amplification of its fusion transcripts, which can be quantified by competitive PCR and similar assays for assessment of residual disease in the follow-up of therapy. In the great majority of CML patients the BCR-ABL transcripts exhibit a b2a2 and/or a b3a2 junction; in rare cases, the only detectable BCR-ABL transcripts have unusual junctions, such as b2a3, b3a3, e1a2 or e6a2. There is a recent suggestion that the BCR-ABL gene may not be always 'functional', since extremely low levels of BCR-ABL transcripts can be found in leucocytes from normal individuals and, conversely, it appears that no BCR-ABL transcription can be detected in a proportion of Ph-positive haematopoietic progenitors from some CML patients. The role, if any, of the reciprocal ABL-BCR hybrid gene in CML is unknown. Although its mRNA message is in frame, no ABL-BCR fusion protein has yet been identified in CML patients. The blast crisis of CML has been variably associated with abnormalities of proto-oncogenes, such as RAS and MYC, or of tumour suppressor genes, in particular RB, p53 and p16, or with the generation of chimeric transcription factors, as in the AML1-EVI1 gene fusion. It is likely, therefore, that multiple and alternative molecular defects, as opposed to a single universal mechanism, underlie the acute transformation of the disease.

Publication types

  • Review

MeSH terms

  • Blast Crisis / genetics
  • Blast Crisis / pathology
  • Cell Transformation, Neoplastic / genetics
  • Chromosomes, Human, Pair 22 / genetics
  • Chromosomes, Human, Pair 22 / ultrastructure
  • Chromosomes, Human, Pair 9 / genetics
  • Chromosomes, Human, Pair 9 / ultrastructure
  • Clone Cells / pathology
  • Exons / genetics
  • Fusion Proteins, bcr-abl / genetics*
  • Fusion Proteins, bcr-abl / physiology
  • Gene Expression Regulation, Leukemic*
  • Genes, abl
  • Genomic Imprinting
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / physiology
  • Oncogenes
  • Philadelphia Chromosome


  • Neoplasm Proteins
  • Fusion Proteins, bcr-abl