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lüll Role of transforming growth factor-beta in hematologic malignancies Dong M; Blobe GCBlood 2006[Jun]; 107 (12): 4589-96The 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.|*Cell Differentiation/drug effects/genetics[MESH]|*Hematopoiesis/drug effects/genetics[MESH]|*Signal Transduction/drug effects/genetics[MESH]|Animals[MESH]|Cell Movement/drug effects/genetics[MESH]|Cell Proliferation/drug effects[MESH]|Drug Resistance, Neoplasm/drug effects/genetics[MESH]|Hematologic Neoplasms/drug therapy/genetics/*metabolism/pathology[MESH]|Humans[MESH]|Mutation/drug effects[MESH]|Oncogene Proteins/genetics/*metabolism[MESH]|Transforming Growth Factor beta/genetics/*metabolism[MESH] |