The role of stem cell factor SALL4 in leukemogenesis.
The role of stem cell factor SALL4 in leukemogenesis.
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DOI：
10.1615/critrevoncog.v16.i1-2.110
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发表时间：
2011
影响因子：
--
通讯作者：
Chai L
中科院分区：
文献类型：
--
作者：
Gao C;Kong NR;Chai L
SALL 4是萨尔基因家族的成员之一，是干细胞最重要的转录调控因子之一。干细胞生物学家对它特别感兴趣，因为它与胚胎干细胞（ESC）和造血干细胞（HSC）的自我更新有关，并参与人类白血病。在ESC中，Sall 4/Oct 4/Nanog核心转录网络控制人和鼠ESC的自我更新和多能性。在正常HSC和白血病干细胞（LSC）中，SALL 4与参与自我更新的三种已知途径相关：Wnt/β-连环蛋白、Bmi-1和Pten。尽管SALL 4在HSC和LSC的自我更新中具有重要的共同作用，但我们最近通过关联全局下游靶基因和在正常细胞与白血病细胞中的独特功能研究获得的研究表明，SALL 4对正常细胞和白血病细胞中的促凋亡和抗凋亡途径具有不同的作用。靶向SALL 4，特别是当与BCL 2拮抗剂ABT-737联合使用时，可能导致白血病细胞特异性凋亡。本文综述了萨尔基因家族的研究进展，特别是SALL 4在干细胞、发育以及肿瘤发生，特别是白血病发生中的作用
SALL4, a member of SALL gene family, is one of the most important transcriptional regulators of stem cells. It is of particular interest to stem cell biologists because it is linked to the self-renewal of both embryonic stem cells (ESCs) and hematopoietic stem cells (HSCs), as well as involved in human leukemia. In ESCs, the Sall4/Oct4/Nanog core transcriptional network governs the self-renewal and pluripotent properties of human and murine ESCs. In normal HSCs and leukemic stem cells (LSCs), SALL4 is linked to three known pathways that are involved in self-renewal: Wnt/β-catenin, Bmi-1 and Pten. Despite the important shared role of SALL4 in self-renewal of HSCs and LSCs, our recent studies obtained through correlating global downstream target genes and unique functional studies in normal versus leukemic cells have demonstrated that SALL4 has differential effects on both pro- and anti-apoptotic pathways in normal and leukemic cells. Targeting SALL4, particularly when combined with the use of ABT-737, a BCL2 antagonist, could lead to leukemic cell-specific apoptosis. This review summarizes our current knowledge on the SALL gene family, particularly on the role of SALL4 in stem cells, development as well as tumorigenesis, especially leukemogenesis