Gamou T, Kitamura E, Hosoda F, Shimizu K, Shinohara K, Hayashi Y, Nagase T, Yokoyama Y, Ohki M
Radiobiology Division, National Cancer Center Research Institute, Tokyo, Japan.
Blood. 1998 Jun 1;91(11):4028-37.
The t(16;21)(q24;q22) translocation is a rare but recurrent chromosomal abnormality associated with therapy-related myeloid malignancies and a variant of the t(8;21) translocation in which the AML1 gene on chromosome 21 is rearranged. Here we report the molecular definition of this chromosomal aberration in four patients. We cloned cDNAs from the leukemic cells of a patient carrying t(16;21) by the reverse transcription polymerase chain reaction using an AML1-specific primer. The structural analysis of the cDNAs showed that AML1 was fused to a novel gene named MTG16 (Myeloid Translocation Gene on chromosome 16) which shows high homology to MTG8 (ETO/CDR) and MTGR1. Northern blot analysis using MTG16 probes mainly detected 4.5 kb and 4.2 kb RNAs, along with several other minor RNAs in various human tissues. As in t(8;21), the t(16;21) breakpoints occurred between the exons 5 and 6 of AML1, and between the exons 1 and 2 or the exons 3 and 4 of MTG16. The two genes are fused in-frame, resulting in the characteristic chimeric transcripts of this translocation. Although the reciprocal chimeric product, MTG16-AML1, was also detected in one of the t(16;21) patients, its protein product was predicted to be truncated. Thus, the AML1-MTG16 gene fusion in t(16;21) leukemia results in the production of a protein that is very similar to the AML1-MTG8 chimeric protein.
t(16;21)(q24;q22)易位是一种罕见但反复出现的染色体异常，与治疗相关的髓系恶性肿瘤相关，是t(8;21)易位的一种变体，其中21号染色体上的AML1基因发生重排。在此，我们报告了4例患者中这种染色体畸变的分子定义。我们使用AML1特异性引物，通过逆转录聚合酶链反应从一名携带t(16;21)的患者的白血病细胞中克隆了cDNA。对cDNA的结构分析表明，AML1与一个名为MTG16（16号染色体上的髓系易位基因）的新基因融合，该基因与MTG8（ETO/CDR）和MTGR1具有高度同源性。使用MTG16探针的Northern印迹分析主要在各种人类组织中检测到4.5 kb和4.2 kb的RNA，以及其他几种较小的RNA。与t(8;21)一样，t(16;21)的断点发生在AML1的外显子5和6之间，以及MTG16的外显子1和2或外显子3和4之间。这两个基因框内融合，产生了这种易位的特征性嵌合转录本。尽管在一名t(16;21)患者中也检测到了相互的嵌合产物MTG16-AML1，但其蛋白质产物预计会被截断。因此，t(16;21)白血病中的AML1-MTG16基因融合导致产生一种与AML1-MTG8嵌合蛋白非常相似的蛋白质。
