Transforming potential of the T-cell acute lymphoblastic leukemia-associated homeobox genes HOXA13, TLX1, and TLX3
Transforming potential of the T-cell acute lymphoblastic leukemia-associated homeobox genes HOXA13, TLX1, and TLX3
复制标题
DOI：
10.1002/gcc.20348
复制
发表时间：
2006-09-01
影响因子：
3.7
通讯作者：
Lavau, Catherine
中科院分区：
文献类型：
--
作者：
Su, XinYing;Drabkin, Harry;Lavau, Catherine
最近人们认识到HOXA基因在t细胞急性淋巴细胞白血病（TALL）中的重要性。我们报道了一例TALL患者的染色体易位，该易位位于HOXA13基因上游和BCLIIB/ CTIP2位点下游。HOXA基因转录分析显示HOXA13大量表达，而其他HOXA基因未受影响。在第二例患者中观察到与HOXA13特异性表达相关的HOXA位点的基因组重排。这种情况类似于t - all中激活TLXIHOX11家族基因的染色体易位。为了比较HOXA13蛋白与TLX蛋白的致白血病特性，将受致死性照射的小鼠移植到用表达TLX3或HOXA13的逆转录病毒载体转导的骨髓中。移植后的小鼠外周血中检测不到TLX3或HOXA 13转导的细胞，没有小鼠发生恶性肿瘤。HOX辅助因子MEIS1与TLX3或HOXA13的共转导并未改变这一结果。然而，在髓系克隆实验中，HOXA13和TLX3与TLX1类似地延长了祖细胞的增殖。总之，我们的研究结果强烈表明，诱导t细胞白血病发生的绝对需要与同源盒基因上调相关的合作事件。(c) 2006 Wiley-Liss, Inc。
The importance of HOXA genes in T-cell acute lymphoblastic leukemia (TALL) has recently been recognized. We report a novel chromosomal translocation in a TALL patient that maps upstream of the HOXA13 gene and downstream of the BCLIIB/ CTIP2 locus. Analysis of HOXA gene transcription demonstrated massive expression of HOXA13, whereas the other HOXA genes were unaffected. A genomic rearrangement of the HOXA locus associated with exclusive expression of HOXA13 was observed in a second patient. This situation resembles chromosomal translocations activating genes of the TLXIHOX11 family in T-ALLs. To compare the leukemogenic properties of HOXA13 to that of TLX proteins, cohorts of lethally irradiated mice were transplanted with bone marrow transduced with a retroviral vector expressing TLX3 or HOXA13. Cells transduced with TLX3 or HOXA 13 could not be detected in the peripheral blood of mice post-transplantation and none of the mice developed malignancies. Cotransduction of the HOX cofactor MEIS1 with TLX3 or HOXA13 did not alter this outcome. However, in a myeloid clonogenic assay HOXA13 and TLX3 extended the proliferation of progenitors similarly to what was observed for TLX1. Altogether, our results strongly suggest the absolute requirement for cooperative events in association with homeobox gene up-regulation to induce T-cell leukennogenesis. (c) 2006 Wiley-Liss, Inc.