Dong Mei, Blobe Gerard C
Department of Medicine, Duke University Medical Center, Box 2631, Durham, NC 27710, USA.
Blood. 2006 Jun 15;107(12):4589-96. doi: 10.1182/blood-2005-10-4169. Epub 2006 Feb 16.
The transforming growth factor-beta (TGF-beta) signaling pathway is an essential regulator of cellular processes, including proliferation, differentiation, migration, and cell survival. During hematopoiesis, the TGF-beta signaling pathway is a potent negative regulator of proliferation while stimulating differentiation and apoptosis when appropriate. In hematologic malignancies, including leukemias, myeloproliferative disorders, lymphomas, and multiple myeloma, resistance to these homeostatic effects of TGF-beta develops. Mechanisms for this resistance include mutation or deletion of members of the TGF-beta signaling pathway and disruption of the pathway by oncoproteins. These alterations define a tumor suppressor role for the TGF-beta pathway in human hematologic malignancies. On the other hand, elevated levels of TGF-beta can promote myelofibrosis and the pathogenesis of some hematologic malignancies through their effects on the stroma and immune system. Advances in the TGF-beta signaling field should enable targeting of the TGF-beta signaling pathway for the treatment of hematologic malignancies.
转化生长因子-β（TGF-β）信号通路是细胞增殖、分化、迁移和细胞存活等细胞过程的重要调节因子。在造血过程中，TGF-β信号通路是增殖的有效负调节因子，同时在适当的时候刺激分化和凋亡。在包括白血病、骨髓增殖性疾病、淋巴瘤和多发性骨髓瘤在内的血液系统恶性肿瘤中，对TGF-β的这些稳态作用产生了抗性。这种抗性的机制包括TGF-β信号通路成员的突变或缺失以及癌蛋白对该通路的破坏。这些改变确定了TGF-β通路在人类血液系统恶性肿瘤中的肿瘤抑制作用。另一方面，TGF-β水平升高可通过其对基质和免疫系统的影响促进骨髓纤维化和一些血液系统恶性肿瘤的发病机制。TGF-β信号领域的进展应能使针对TGF-β信号通路治疗血液系统恶性肿瘤成为可能。
