TWO STEP MECHANISM FOR FORMATION OF COMPLEX 9;22 CHROMOSOME TRANSLOCATION IN CHRONIC MYELOCYTIC LEUKEMIA DETECTED BY FLUORESCENCE IN SITU HYBRIDIZATION

Tanaka K., Minamihisamatu M., Yagi Sh., Kyo T., Dohy H., Kamada N.

3 to 5% of CML patients show complex translocation involving chromosomes 9, 22 and third chromosome. We analyzed metaphases from fifteen CML patients with complex translocation and three CML patients with normal karyotype by two colors FISH using whole chromosome painting probes, BCR and ABL probe, and several cosmid probes locating near BCR and ABL locus. Thirteen of the 18 patients showed two step translocation (chromosomes 9 to 22 and second translocation between derivative 9 [der(9)] chromosome and third chromosome). Remaining five patients were represented either by one step translocation (chromosomes 9 — 22 — third chromosome) or by insertion of chromosomal segment containing BCR-ABL chimeric gene and second translocation between chromosomes 9 and 22 and third chromosome. Out of the 13 patients, 3 patients had second breakpoint at 9q12, 9q22 and 9q32 on der(9) chromosome, and 9 patients had second breakpoint at telomeric site from the 3'-ABL locus, and 6 patient at telomeric sites at vicinity of the breakpoint of der(22) chromosome between BCR and EWS locus. In 4 patients, loss of 17p13 or 9p12 region was observed on chromosomes 17 and 9 as a third chromosome for formation of complex 9;22 translocation. Loss of the critical region seems to be related to transformation of blastic crisis phase. These results suggest that two step mechanisms are mostly associated with formation of complex 9;22 translocation and the vicinity regions around the breakpoints on both der(9) and der(22) chromosomes have higher genetic instability and are prone to acquire second chromosome aberrations.

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