Persistence of CML Despite Deletion of Rearranged bcr/c-abl Sequences

Abstract

Chronic myelocytic leukemia (CML) is clinically divided into a chronic phase lasting for about 4 years, followed by an acute phase (blast crisis) of a few months’ duration [5]. The cytogenetic hallmark of 95% of CML cases is the Philadelphia (Ph) chromosome, resulting from a reciprocal translocation between chromosomes 9 and 22 [21, 22] that places the c-abl oncogene into the breakpoint cluster region (bcr) on chromosome 22 [7, 11]; this area is part of a gene of yet unknown function [17, 24]. An involvement of c-abl and bcr sequences in the development of Ph-positive CML has been deduced from (a) the consistent rearrangement of both genes in all cytogenetic subtypes of this leukemia [1, 7, 14, 15], (b) the concurrent detection of a novel 8.5-kb hybrid bcr/abl RNA transcript [6, 10, 15], and (c) the expression of an altered c-abl protein that differs from its normal counterpart in having a higher associated tyrosine kinase activity [18, 19].