Characterization of the translocation breakpoint sequences in philadelphia-positive acute lymphoblastic leukemia

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Abstract
We have previously described a patient in whom the breakpoint occurred within the first intron of the BCR gene and have cloned the 9q+ and 22q− junctions. We have now determined the nucleotide sequence around the breakpoints on both translocation products from this patient as well as the corresponding regions from the normal chromosomes 9 and 22. We have compared the sequence with that of the breakpoint regions in the Ph1‐positive leukemic patients in order to check for the presence of conserved motifs. A + T‐rich sequences and ALU repeat elements are the only sequence characteristics which appear to be very common around translocation regions. The chromosome 9 ABL sequences at or adjacent to the breakpoints present in the 22q‐ product show homology to the consensus ALU sequence while the chromosome 22 sequences do not, suggesting a non‐homologous recombination mechanism. While no sequences are deleted, there is a two‐base‐pair “homology” at the junction. Therefore, staggered breaks followed by ligation and repair could be part of the mechanism involved in the process of translocation in some cases of Ph1‐positive ALL.