Chromosomal breakpoints within the first intron of the ABL gene are nonrandom in patients with chronic myelogenous leukemia

Bone marrow cells from 37 patients with chronic myelogenous leukemia (CML), who had the characteristic Philadelphia chromosome in their leukemic cells, were examined for ABL gene rearrangement by pulsed- field gel electrophoresis. By using several probes from the ABL gene, we found that in 33 of 37 (89%) patients studied, the translocation breakpoints in ABL fell within the 175-kilobase (kb) intron between exons 1b and 1a. Furthermore, breakpoints in this intron clustered in three regions, approximately 30 +/- 5, 100 +/- 13, and 135 +/- 8 kb downstream from exon 1b. These findings suggest that there may be specific sequences in this intron that facilitate the processes of chromosomal translocation.