The molecular biology of chronic myeloid leukaemia.

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