Alu and translisin recognition site sequences flanking translocation sites in a novel type of chimeric bcr-abl transcript suggest a possible general mechanism for bcr-abl breakpoints

Background and Objectives. We further characterized a novel type of chimeric BCR-ABL mRNA transcript detected in a patient with Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML). Design and Methods. We used reverse-transcription polymerase chain reaction (RT-PCR) and sequence analysis of the fusion region of the amplified cDNA fragment. Western analysis was performed on total Results. Part of exon e8 of the BCR gene was joined to an intronic sequence of ABL intron Ib spliced on exon a2 of the ABL gene, giving rise to an in-frame e8-int-a2 BCR-ABC transcript. Only part of exon 8 of the BCR gene (e8)(intra-exonic break) was retained. The consequent BCR-int-ABL transcript was translated into a BCR-ABL protein of 1804 amino acid residues with a molecular mass of 197.5 kilodaltons (kDa) called p200 BCR-ABL. The 3' part of bcr exon 8 recombined within or alongside Alu elements at the additional sites. Sequence motifs similar to consensus binding sites of the lymphoid-associated TRAX and translisin proteins were present on both participating strands at 22q11 and 9q34 recombination sites, respectively. No differences in clinical or laboratory findings at diagnosis were found between this patient and CML patients with bcr-abl fusion. Interpretation and Conclusions. The presence of Alu sequences and of the translisin binding motif on both sides of the breaks in this novel translocation suggests a possible general mechanism of molecular recombination in CML patients. (C) 2000 Ferrata Storti Foundation.