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

TLDR

BCR/ABL rearrangement is the hallmark of chronic myelogenous leukaemia, occurs in only about 1 % of acute myeloid leukaemia cases, and is usually driven by breakpoints in the major breakpoint cluster region; micro‑breakpoint cases are rare and have been linked mainly to mild Philadelphia‑chromosome‑positive chronic neutrophilic leukaemia. The study reports an acute myeloid leukaemia case with a micro‑bcr (e19a2) BCR/ABL rearrangement detected by RT‑PCR. RT‑PCR was employed to identify the micro‑bcr breakpoint in the patient’s leukemic cells. Cytogenetic analysis revealed progression to a blast‑crisis‑like clone with two Ph chromosomes, trisomy 8, isochromosome 17q, and 7q deletion, and immunoprecipitation showed constitutive activation of an abnormal P230 BCR/ABL protein, highlighting the protein’s role in diverse leukaemia phenotypes.

Abstract

The BCR/ABL rearrangement, the molecular hallmark of chronic myelogenous leukaemia (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 the micro bcr region have so far been reported. The micro breakpoint position has been associated mainly with a mild form of CML, defined as Philadelphia chromosome‐positive chronic neutrophilic leukaemia (Ph‐positive CNL). Using reverse transcription‐polymerase chain reaction (RT‐PCR) we report a patient with an acute myeloid leukaemia phenotype at diagnosis who showed a BCR/ABL rearrangement with a breakpoint located in the micro bcr region (e19a2 junction). Cytogenetic analysis showed a progression of the malignant clone, finally leading to cells with two Ph chromosomes, trisomy 8, isochromosome 17q and deletion of the long arms of chromosome 7. The findings of chromosomal changes point to a possibility of blast crisis of CML with a clinically silent chronic phase. Immunoprecipitation and auto‐phosphorylation assay revealed the expression, by the patient's blast cells, of an abnormal P230 BCR/ABL protein, which showed for the first time that this protein was constitutively activated in primary cells from patients. This finding may contribute 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.