THE FIRST INTRON OF THE BCR GENE CONTAINS 2 MINOR ALTERNATIVE EXONS

In Philadelphia chromosome (Ph(1)) positive leukemias, the BCR gene is fused to the ABL gene. The resulting chimeric BCR-ABL oncoproteins ar e thought to play a central role in the pathogenesis of these diseases . We previously described two exons that can be spliced alternatively to the second BCR exon in place of the first exon to form minor messag es. In this paper, we localize the alternative exons to a 4.1 kb BglII fragment in the 5' region of the large first intron of the BCR gene. This genomic structure is of interest because of its analogy to the or ganization of the ABL gene and because this part of the gene is not af fected by the breakpoints occurring in Ph(1)-positive acute lymphoblas tic leukemia (ALL). Using the reverse transcriptase-polymerase chain r eaction (RT-PCR), we detected the alternative messages in all cases of chronic myelogenous leukemia (CML) tested, including seven samples in the chronic phase, five in the accelerated phase and nine in the acut e phase, as well as in the majority of other samples studied. These fi ndings suggest a functional role for the variant transcripts.