Review in translational hematology Role of transforming growth factor- in hematologic malignancies

The transforming growth factor(TGF) signaling pathway is an essential regulator of cellular processes, including proliferation, differentiation, migration, and cell survival. During hematopoiesis, the TGFsignaling 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 TGFdevelops. Mechanisms for this resistance include mutation or deletion of members of the TGFsignaling pathway and disruption of the pathway by oncoproteins. These alterations define a tumor suppressor role for the TGFpathway in human hematologic malignancies. On the other hand, elevated levels of TGFcan promote myelofibrosis and the pathogenesis of some hematologic malignancies through their effects on the stroma and immune system. Advances in the TGFsignaling field should enable targeting of the TGFsignaling pathway for the treatment of hematologic malignancies. (Blood. 2006; 107:4589-4596)