Transforming growth factor-beta signaling in normal and malignant hematopoiesis

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