Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal.
UMR967 INSERM/CEA, équipe labellisée Ligue Nationale contre le Cancer, Fontenay-aux-Roses, France.
Leukemia. 2016 Oct;30(10):1968-1978. doi: 10.1038/leu.2016.169. Epub 2016 Jun 13.
TAL1/SCL/TCL5 is a critical transcription factor for hematopoietic stem cell maintenance and regulation of early hematopoiesis. However, aberrant expression of TAL1 in committed T-cell precursors is also directly implicated in the development of T-cell leukemia. Roughly 25 years ago TAL1 was identified in early hematopoietic cells and involved in leukemia. Here, we review the wealth of knowledge gained since then on its physiological roles and mechanisms by which TAL1 ectopic expression contributes to leukemogenesis. We emphasize recent findings that shed light into the intricacies of TAL1 (epi)genetic regulation and the transcription network orchestrated by this major T-cell oncogene. Importantly, an exciting time is coming when data using the mechanistic knowledge accumulated on TAL1 may be used to develop novel anti-leukemia targeted therapies.
TAL1/SCL/TCL5 是造血干细胞维持和早期造血调控的关键转录因子。然而,TAL1 在定向 T 细胞前体中的异常表达也直接涉及 T 细胞白血病的发生。大约 25 年前,TAL1 在早期造血细胞中被鉴定出来,并与白血病有关。在这里,我们回顾了自那时以来获得的关于其生理作用以及 TAL1 异位表达促进白血病发生的机制的大量知识。我们强调了最近的发现,这些发现揭示了 TAL1 的复杂性(表观遗传学调控)以及由这个主要的 T 细胞癌基因协调的转录网络。重要的是,当使用在 TAL1 上积累的机制知识来开发新的靶向白血病的治疗方法时,激动人心的时刻即将到来。