Miyoshi H, Shimizu K, Kozu T, Maseki N, Kaneko Y, Ohki M
Department of Immunology and Virology, Saitama Cancer Center Research Institute, Japan.
Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10431-4. doi: 10.1073/pnas.88.23.10431.
The t(8;21)(q22;q22) translocation is a non-random chromosomal abnormality frequently found in patients with acute myeloid leukemia (AML) with maturation (M2 subtype). We report here the cloning of a gene, named AML1, on chromosome 21 that was found to be rearranged in the leukemic cell DNAs from t(8;21) AML patients. The breakpoints in 16 out of 21 patients were clustered within a limited region of AML1, and detailed analysis in 3 patients revealed that the breakpoints occurred in the same intron of the gene. Sequencing of cDNA clones identified a long open reading frame encoding a 250-amino acid protein. Northern blot analysis detected four constant mRNA species in t(8;21) leukemic and normal cells; the largest species was more abundant in the leukemic cells than in normal cells. In addition, two mRNA species limited to the leukemic cells were found. These findings indicate that the AML1 gene may be involved in neoplastic transformation of AML with the t(8;21) translocation.
t(8;21)(q22;q22)易位是一种非随机染色体异常，常见于急性髓系白血病（AML）伴成熟型（M2亚型）患者。我们在此报告在21号染色体上克隆的一个名为AML1的基因，该基因在t(8;21) AML患者的白血病细胞DNA中发生了重排。21例患者中有16例的断点聚集在AML1的一个有限区域内，对3例患者的详细分析表明，断点发生在该基因的同一个内含子中。cDNA克隆测序鉴定出一个编码250个氨基酸蛋白质的长开放阅读框。Northern印迹分析在t(8;21)白血病细胞和正常细胞中检测到四种恒定的mRNA种类；最大的种类在白血病细胞中比在正常细胞中更丰富。此外，还发现了两种仅限于白血病细胞的mRNA种类。这些发现表明，AML1基因可能参与了t(8;21)易位的AML的肿瘤转化。
