Heterogeneity of the breakpoint in the ABL gene in cases with BCR/ABL transcript lacking ABL exon a2

We report cases with a variant BCR/ABL mRNA expression lacking ABL exon a2 sequences. Two of these cases showed major breakpoint cluster region (BCR) exon 3 (b3) and ABL exon 3 (a3) junction (b3/a3), while the other case showed minor BCR exon 1 (e1) and a3 junction (e1/a3). One of the two cases with b3/a3 junction and the case with e1/a3 junction were diagnosed as acute lymphoblastic leukemia, and the remaining case with b3/a3 junction was chronic myeloid leukemia. Two of these cases, however, were found to have a breakpoint in the ABL gene outside of the intron between exons a2 and a3, probably 5' upstream of exon a2, suggesting that the BCR exon was spliced to ABL exon a3. These findings differ from those previously reported, in which the breakpoints in the ABL gene were between exons a2 and a3, and indicate a novel mechanism for the deletion of ABL exon a2 sequences in the formation of a variant BCR/ABL fusion transcript. The significance of the finding that a part of the SH3 region of ABL protein is missing in some Philadelphia chromosome-positive leukemias is discussed in reference to the cases reported previously.