Transforming growth factor-β signaling in normal and malignant hematopoiesis

被引：103

作者：

Kim, SJ ^{[1
]}

Letterio, J ^{[1
]}

机构：

[1] NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA

来源：

LEUKEMIA | 2003年 / 17卷 / 09期

关键词：

transforming growth factor-beta (TGF-beta); TGF-beta receptors; Smad; leukemogenesis; hematopoiesis; CDK inhibitors; human T-cell lymphotropic virus type I (HTLV-I);

D O I：

10.1038/sj.leu.2403069

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Transforming growth factor-beta (TGF-beta) is perhaps the most potent endogenous negative regulator of hematopoiesis. The intracellular signaling events mediating the effects of TGF-beta are multiple, involving extensive crosstalk between Smad-dependent and MAP-kinase-dependent pathways. We are only beginning to understand the importance of the balance between these cascades as a determinant of the response to TGF-beta, and have yet to determine the roles that disruption in TGF-beta signaling pathways might play in leukemogenesis. This review summarizes current knowledge regarding the function of TGF-beta in normal and malignant hematopoiesis. The principal observations made by gene targeting studies in mice are reviewed, with an emphasis on how a disruption of this pathway in vivo can affect blood cell development and immune homeostasis. We overview genetic alterations that lead to impaired TGF-beta signaling in hematopoietic neoplasms, including the suppression of Smad-dependent transcriptional responses by onco-proteins such as Tax and Evi-1, and fusion proteins such as AML1/ETO. We also consider mutations in genes encoding components of the core cell cycle machinery, such as p27(Kip1) and p15(INK4A), and emphasize their impact on the ability of TGF-beta to induce G1 arrest. The implications of these observations are discussed, and opinions regarding important directions for future research on TGF-beta in hematopoiesis are provided.

引用

页码：1731 / 1737

页数：7

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