Leukemia-related Bcr-abl Gene Sequence Analysis

The Philadelphia chromosome is found in more than 90% of patients with chronic myeloid leukemia(CML) and 30% of patients with acute lymphoblastic leukemia(ALL). These patients generally display a reciprocal translocation between chromosome 9 and 22[t(9;22)(q34;ql 1)], involving the bcr gene on the 22q1 1 region and the abl gene on the 9q34 region. The translocation results in the head-to-tail fusion of the bcr and abl gene. However, the specific recombination mechanism of t(9;22) translocation in still unknown. The structural figure of the bcr-abl fusion gene suggests a possible relationship between molecular recombination and retroelements. In order to explore the relationship between molecular recombination and retroelements, we analysis the bcr abl gene. At first, we compare the bcr^. abl genome sequenced from normal cells by the Human Genome Project and from CML cells; A Multiple sequences alignment of the sequences around the breakpoints of the fusion gene is taken for the sake of search for the specific conservative motif recognized by the recombinases. The bcr abl gene sequences are searched from the Genebank database. We use BLAST and DOT PLOT to compare the bcr abl genome sequenced from normal cells by the HGP and from CML cell. Most importantly, there 4 are two additional segments compared with HSABLGR3, the abl genome sequenced from CML cell and the HGP sequences NT₀08338.3 and NT₀08338.2. We found clusters of Alu elements and five breakpoint site in the two segments and three breakpoint site are inside the Alu elements. This result suggests a significant relationship between the molecular recombination and the Alu elements. We further detect a distinctness between different abl genome whish are sequenced from different cell. Multiple sequences alignment is obtained with MACAW program provided by NCBI. A consensus sequence CCCAG is found On both gene, 5?bcr gene and 5?abl breakpoint region which is be likely to the specific consensus motif recognized by the recombinases. We didn抰 find the specific recombination signal sequence(RSS) of the V(D)J recombination and also the consensus sequence TGCAG-N(0-4bp)-GCCC homology with translisin. Two additional segments of the HSABLGR1 gene suggests a possible general mechanism of molecular recombination in Ph chromosome.