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

✍ Scribed by Dr. Panos C. Papadopoulos; Amy M. Greenstein; Robert A. Gaffney; Carol A. Westbrook; Leanne M. Wiedemann

• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: English
• Weight: 686 KB
• Volume: 1
• Category: Article
• ISSN: 1045-2257
• DOI: 10.1002/gcc.2870010308

✦ Synopsis

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 Ph'-positive leukemic patients in order t o check for the presence of conserved motifs. A + T-rich sequences and ALU repeat elements are the only sequence characteristics which appear t o be very common around translocation regions. The chromosome 9 ABL sequences at or adjacent to the breakpoints present in the 22q-product show homology t o 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 Phi-positive ALL.