The diversity of BCR-ABL fusion proteins and their relationship to leukemia phenotype.

Abstract

HE PHILADELPHIA (Ph) chromosome was the first T chromosomal abnormality associated with a specific malignant disease in humans, namely chronic myeloid leukemia (CML).’ Later it was identified as one partner in a reciprocal translocation between chromosomes 9 and 22, referred to as t(9;22)(q34;q11).2 We know now that this translocation results in the formation of two hybrid genes, BCR-ABL on the Ph chromosome and ABL-BCR on 9q+. The BCR-ABL gene encodes a fusion protein with elevated tyrosine kinase activity3 which is regarded as central to the mechanism that underlies the chronic phase of CML.435 The role, if any, of the reciprocal fusion gene, ABL-BCR, remains u n k n ~ w n . ~ * ~ More than 95% of patients with clinically ‘acceptable’ CML have a BCR-ABL gene in their leukemia cells,8 so the t(9;22) can generally be regarded as the hallmark of CML. However, it is not exclusive to CML because it is found in 10% to 20% of adults’ and in 2% to 5% of children’0,’’ with acute lymphoblastic leukemia (ALL), as well as in occasional bona fide cases of acute myeloid leukemia (AML),’2-’6 and mye10ma.2”22 In the current issue of Blood, Pane et a123 add to this list a new disease entity, namely Ph’ chronic neutrophilic leukemia (CNL), with a novel position for the breakpoint in the BCR gene. They bring into focus the fascinating suggestion that the precise location of the breakpoint in BCR (and in ABL), and thus the composition of the fusion BCR-ABL protein, may determine the disease phenotype.

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@article{Melo1996TheDO, title={The diversity of BCR-ABL fusion proteins and their relationship to leukemia phenotype.}, author={J V Melo}, journal={Blood}, year={1996}, volume={88 7}, pages={2375-84} }