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t(1;3)(p36;p21) is a recurring therapy‐related translocation

2002; Wiley; Volume: 34; Issue: 2 Linguagem: Inglês

10.1002/gcc.10055

1098-2264

Yuko Sato, Tohru Izumi, Hirakazu Kanamori, Elizabeth M. Davis, Yasusada Miura, Richard A. Larson, Michelle M. Le Beau, Keiya Ozawa, Janet D. Rowley,

Lung Cancer Treatments and Mutations

Abstract Chromosome bands 1p36 and 3p21 are known to be recurring breakpoints in therapy‐related (t‐) leukemia. We identified a recurring translocation, t(1;3)(p36;p21), in eight patients with various hematologic malignancies: three patients with ALL, one with chronic myelogenous leukemia (CML) in accelerated phase (AP), two with MDS, and two with AML(M3). Five of the eight patients had a history of chemotherapy, including alkylating agents in three, before the translocation was detected. In two of these five patients, the t(1;3)(p36;p21) emerged only at relapse or in the accelerated phase of CML. The karyotypes of the patients were complex, including −7 and structural abnormalities of 5q, 6q, 7q, 9p, and 11q23. Survival time varied among patients (25 days to more than 16 years). Using FISH with 13 1p35–36 cosmid probes (tel—FB12–CA5–G7–FD2–CB1–ED8–FD9–G32–AE3–G50–AD8–GG4–G43—cen), we delineated the 1p36 breakpoint in two patients with MDS and ALL as lying between FB12 and FD2 (between BAC47P3 and PAC963K15), with a small deletion near the breakpoint in both cases. In the patient with MDS, there was also a deletion at 3p21.3, as detected with the cosmid probe cosNRL9. The results of the present study suggest that t(1;3)(p36;p21) in hematologic diseases is associated with prior exposure to mutagens, including alkylating agents. © 2002 Wiley‐Liss, Inc.