Rice Kim L, Izon David J, Ford Jette, Boodhoo Alvin, Kees Ursula R, Greene Wayne K
School of Veterinary and Biomedical Sciences, Division of Health Sciences, Murdoch University, South Street, Murdoch, Perth WA 6150, Australia.
Leuk Res. 2008 Jun;32(6):873-83. doi: 10.1016/j.leukres.2007.11.001. Epub 2007 Dec 21.
TLX1/HOX11 is an oncogenic transcription factor in human T-cell leukemia, however, the molecular basis for its transforming activity has remained elusive. The ALDH1A1 gene, whose product participates in retinoic acid synthesis, was previously identified as a TLX1-responsive gene. Here, we confirm regulation of ALDH1A1 transcription by TLX1 and show that ALDH1A1 can profoundly perturb murine hematopoiesis by promoting myeloid differentiation at the expense of lymphopoiesis. Together, these data demonstrate that ALDH1A1 plays a key role in normal hematopoiesis, and confirm ALDH1A1 as a TLX1 transcriptional target that may contribute to the ability of this homeoprotein to alter cell fate and induce tumor growth.
TLX1/HOX11是人类T细胞白血病中的一种致癌转录因子，然而，其转化活性的分子基础一直难以捉摸。ALDH1A1基因的产物参与视黄酸合成，该基因先前被鉴定为TLX1反应基因。在此，我们证实了TLX1对ALDH1A1转录的调控，并表明ALDH1A1可通过促进髓系分化而以淋巴细胞生成受损为代价，严重扰乱小鼠造血。这些数据共同表明，ALDH1A1在正常造血中起关键作用，并证实ALDH1A1是TLX1的转录靶点，可能有助于这种同源蛋白改变细胞命运和诱导肿瘤生长的能力。
