Role of transforming growth factor-beta in hematologic malignancies.
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.
Dong
Mei
M
Department of Medicine, Duke University Medical Center, Box 2631, Durham, NC 27710, USA.
Blobe
Gerard C
GC
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006410:Hematopoiesis / Q000187:drug effects / Q000235:genetics; D006801:Humans; D009154:Mutation / Q000187:drug effects; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D015513:Oncogene Proteins; D016212:Transforming Growth Factor beta