FUSION OF THE TEL GENE ON 12P13 TO THE AML1 GENE ON 21Q22 IN ACUTE LYMPHOBLASTIC-LEUKEMIA
FUSION OF THE TEL GENE ON 12P13 TO THE AML1 GENE ON 21Q22 IN ACUTE LYMPHOBLASTIC-LEUKEMIA
复制标题
DOI：
10.1073/pnas.92.11.4917
复制
发表时间：
1995-05-23
影响因子：
11.1
通讯作者：
GILLILAND, DG
中科院分区：
文献类型：
--
作者：
GOLUB, TR;BARKER, GF;GILLILAND, DG
涉及12p13带的染色体重排在多种人类白血病中发现，但在儿童急性淋巴细胞性白血病中尤其常见，但参与这些重排的基因尚未确定。我们现在报道在两例儿童前B急性淋巴细胞白血病中克隆了涉及12p13和21q22的t(12；21)易位断裂点，其中t(12；21)重排最初并不明显，易位的结果是ETS样转录因子TEL的螺旋-环-螺旋结构域与转录因子AML1的DNA结合域和反活化域融合。这些数据表明，先前在慢性髓单核细胞白血病中与血小板衍生生长因子受体β融合的TEL可通过其与受体酪氨酸激酶或转录因子的融合而参与白血病的发病。TEL-AML1融合还表明，影响AML1基因的易位可能与淋巴系和髓系恶性肿瘤有关。
Chromosomal rearrangements involving band 12p13 are found in a wide variety of human leukemias but are particularly common in childhood acute lymphoblastic leukemia, The genes involved in these rearrangements, however, have not been identified. We now report the cloning of a t(12;21) translocation breakpoint involving 12p13 and 21q22 in two cases of childhood pre-B acute lymphoblastic leukemia, in which t(12;21) rearrangements were not initially apparent, The consequence of the translocation is fusion of the helix-loop-helix domain of TEL, an ETS-like putative transcription factor, to the DNA-binding and transactivation domains of the transcription factor AML1, These data show that TEL, previously shown to be fused to the platelet-derived growth factor receptor beta in chronic myelomonocytic leukemia, can be implicated in the pathogenesis of leukemia through its fusion to either a receptor tyrosine kinase or a transcription factor. The TEL-AML1 fusion also indicates that translocations affecting the AML1 gene can be associated with lymphoid, as well as myeloid, malignancy.