Sequence Analysis of the Breakpoint Cluster Region in the ALL-i Gene Involved in Acute Leukemia'

DNA rearrangements caused by chromosometranslocations between band 11q23 and various chromosomes can be detected by a single probe, B859, an 859-base pair complementary DNA fragment derived from the human ALL-i gene. To try to understand why band 11q23 becomes a frequent target ofthe translocatlons,we have sequencedthe entire break point cluster region, a 8342-base pair BamHI genomic fragment delin eated by 11859.We found eightAlu repeats located within this region in the same orientation as theALL-1 gene. We have also analyzed the sequences of the breakpoints in 10 patIents with 6 different types of 11q23 aberra tion. In five patients the breaks coincided with Alassequences on chromo some 11, but not on the partner chromosomes.Also, sevenof the breaks occurred in the region delineated by exons 6 and 7, which is composed mainly ofAlu sequences. Ia three patients topoisomerase H recognition site-like sequences, at different stringency levels, were identified at the breakpoints on chromosome 11. We conclude that while there is no specificsequenceelement present at all the breakpoints, the high density ofAlu sequences in the breakpoint cluster region possibly makes the latter more prone to recombinationevents.