Core binding factor at the crossroads: determining the fate of the HSC.
Core binding factor at the crossroads: determining the fate of the HSC.
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DOI：
10.1002/jcp.21950
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发表时间：
2010-01
影响因子：
5.6
通讯作者：
Mulloy, James C.
中科院分区：
文献类型：
--
作者：
Link, Kevin A.;Chou, Fu-Sheng;Mulloy, James C.
造血发育需要多种转录因子的协调作用。核心结合因子（CBF）由Runx蛋白和CBFβ蛋白组成，是造血干细胞（HSC）从内皮细胞阶段出现所必需的转录因子复合物。在Runx1或CBFβ基因敲除小鼠中观察到的造血缺陷强调了这种复合物对于确定性造血的必要性。尽管在建立确定的造血过程中需要CBF，但Runx 1缺失对出生后维持HSC状态的影响很小，而CBFβ可能仍然是必需的。血统承诺，另一方面，是显着影响CBF损失在成人，这表明一个主要的作用，这个复杂的调制分化。考虑到造血系统中正常CBF功能的影响，通过点突变或产生融合基因破坏CBF活性的严重后果是显而易见的。CBF在分化中的生理作用被遗传畸变颠覆为自我更新维持的主动过程，通过几种可能的机制，促进造血系统恶性肿瘤的发展，包括骨髓增生异常综合征和白血病。CBF对造血系统在发育和疾病中的主要影响突出了理解这种复杂功能的必要性，并重申继续努力确定CBF相关疾病治疗干预的潜在点的必要性。
Hematopoietic development requires coordinated actions from a variety of transcription factors. The core binding factor (CBF), consisting of a Runx protein and the CBFβ protein, is a transcription factor complex that is essential for emergence of the hematopoietic stem cell (HSC) from an endothelial cell stage. The hematopoietic defects observed in either Runx1 or CBFβ knockout mice underscore the necessity of this complex for definitive hematopoiesis. Despite the requirement for CBF in establishing definitive hematopoiesis, Runx1 loss has minimal impact on maintaining the HSC state postnatally, while CBFβ may continue to be essential. Lineage commitment, on the other hand, is significantly affected upon CBF loss in the adult, indicating a primary role for this complex in modulating differentiation. Given the impact of normal CBF function in the hematopoietic system, the severe consequences of disrupting CBF activity, either through point mutations or generation of fusion genes, are obvious. The physiologic role of CBF in differentiation is subverted to an active process of self-renewal maintenance by the genetic aberrations, through several possible mechanisms, contributing to the development of hematopoietic malignancies including myelodysplastic syndrome and leukemia. The major impact of CBF on the hematopoietic system in both development and disease highlights the need for understanding the intricate functions of this complex and reiterate the necessity of continued efforts to identify potential points of therapeutic intervention for CBF-related diseases.
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影响因子：
64.8
作者：
Chen, Michael J.;Yokomizo, Tomomasa;Zeigler, Brandon M.;Dzierzak, Elaine;Speck, Nancy A.
通讯作者：
Speck, Nancy A.
影响因子：
64.5
作者：
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通讯作者：
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影响因子：
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作者：
Huang, Gang;Zhang, Pu;Tenen, Daniel G.
通讯作者：
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影响因子：
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作者：
Ichikawa, M;Asai, T;Kurokawa, M
通讯作者：
Kurokawa, M
DOI：
10.1073/pnas.0810558106
发表时间：
2009-02-24
影响因子：
11.1
作者：
Kwok, Colin;Zeisig, Bernd B.;So, Chi Wai Eric
通讯作者：
So, Chi Wai Eric