P230 BCR/ABL protein may be associated with an acute leukaemia phenotype

The BCR/ABL rearrangement, the molecular hallmark of chronic myelogenous le ukaemia (CML), is rare in acute myeloid leukaemia (AML), being detected in approximately 1% of cases. In the vast majority of CML cases the breakpoint on chromosome 22 falls in the so-called major breakpoint cluster region of the BCR gene. Only a few cases of CML with breakpoint in the minor or in t he micro bcr region have so far been reported. The micro breakpoint positio n has been associated mainly with a mild form of CML, defined as Philadelph ia chromosome-positive chronic neutrophilic leukaemia (Ph-positive CNL). Us ing reverse transcription-polymerase chain reaction (RT-PCR) we report a pa tient with an acute myeloid leukaemia phenotype at diagnosis who showed a B CR/ABL rearrangement with a breakpoint located in the micro bcr region (e19 a2 junction). Cytogenetic analysis showed a progression of the malignant cl one, finally leading to cells with two Ph chromosomes, trisomy 8, isochromo some 17q and deletion of the long arms of chromosome 7. The findings of chr omosomal changes point to a possibility of blast crisis of CML with a clini cally silent chronic phase, Immunoprecipitation and auto-phosphorylation as say revealed the expression, by the patient's blast cells, of an abnormal P 230 BCR/ABL protein, which showed for the first lime that this protein was constitutively activated in primary cells from patients. This finding may c ontribute to the understanding of the role of the BCR/ABL rearrangements in determining different leukaemia phenotypes ranging from acute lymphoid and myeloid leukaemias to mild chronic neutrophilic leukaemias.