HETEROGENEITY OF THE BREAKPOINT IN THE ABL GENE IN CASES WITH BCR ABLTRANSCRIPT LACKING ABL EXON A2/

We report cases with a variant BCR/ABL mRNA expression lacking ABL exo n a2 sequences. Two of these cases showed major breakpoint cluster reg ion (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 o f the two cases with b3/a3 junction and the case with e1/a3 junction w ere 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 th e intron between exons a2 and a3, probably 5' upstream of exon a2, sug gesting that the BCR exon was spliced to ABL exon a3. These findings d iffer 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 varian t BCR/ABL fusion transcript. The significance of the finding that a pa rt of the SH3 region of ABL protein is missing in some Philadelphia ch romosome-positive leukemias is discussed in reference to the cases rep orted previously.