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.