Deregulated expression of TCL1 causes T cell leukemia in mice.
Deregulated expression of TCL1 causes T cell leukemia in mice.
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TCL1 表达失调会导致小鼠 T 细胞白血病。
DOI：
10.1073/pnas.95.7.3885
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发表时间：
1998
影响因子：
11.1
通讯作者：
Croce,CM
中科院分区：
文献类型：
--
作者：
Virgilio,L;Lazzeri,C;Bichi,R;Nibu,K;Narducci,MG;Russo,G;Rothstein,JL;Croce,CM
人类染色体14q32.1上的TCL1癌基因参与人类T细胞白血病的发生。这些白血病分为 T 幼淋巴细胞白血病（发生于生命晚期）或 T 慢性淋巴细胞白血病（通常发生于年轻时患有共济失调性毛细血管扩张 (AT) 的患者。 TCL1癌基因在这些白血病中通过与T细胞受体的α或β位点并置而被激活，这是由染色体易位t(14:14)(q11:q32)、t(7:14)(q35:q32)或由v(14)(q11:q32)倒位引起的。为了表明TCL1的转录改变与T细胞瘤形成的产生有因果关系，我们已经产生了携带受p56lck启动子元件转录控制的TCL1基因的转基因小鼠。 lck-TCL1转基因小鼠在经过较长潜伏期后发展为成熟T细胞白血病。年轻小鼠出现表达 TCL1 的白血病前 T 细胞扩增，并且白血病仅在年龄较大时发生。鼠白血病的表型是 CD4−CD8+，而人类白血病主要是 CD4+CD8−。这些研究表明TCL1原癌基因的转录激活可引起T淋巴细胞的恶性转化，表明TCL1在T幼淋巴细胞白血病和T慢性淋巴细胞白血病恶性转化的起始中的作用。
TheTCL1oncogene on human chromosome 14q32.1 is involved in the development of T cell leukemia in humans. These leukemias are classified either as T prolymphocytic leukemias, which occur very late in life, or as T chronic lymphocytic leukemias, which often arise in patients with ataxia telangiectasia (AT) at a young age. TheTCL1oncogene is activated in these leukemias by juxtaposition to the α or β locus of the T cell receptor, caused by chromosomal translocations t(14:14)(q11:q32), t(7:14)(q35:q32), or by inversions inv(14)(q11:q32). To show that transcriptional alteration ofTCL1is causally involved in the generation of T cell neoplasia we have generated transgenic mice that carry theTCL1gene under the transcriptional control of the p56lckpromoter element. Thelck-TCL1transgenic mice developed mature T cell leukemias after a long latency period. Younger mice presented preleukemic T cell expansions expressingTCL1, and leukemias developed only at an older age. The phenotype of the murine leukemias is CD4−CD8+, in contrast to human leukemias, which are predominantly CD4+CD8−. These studies demonstrate that transcriptional activation of theTCL1protooncogene can cause malignant transformation of T lymphocytes, indicating the role ofTCL1in the initiation of malignant transformation in T prolymphocytic leukemias and T chronic lymphocytic leukemias.