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PMID: 16484590 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Role of transforming growth factor-beta in hematologic malignancies.

Blood ·Vol. 107 ·No. 12 ·2006-06-15 ·Pages 4589-96

Dong M, Blobe GC

Abstract

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.

MeSH Terms
Animals Cell Differentiation/drug effects,genetics Cell Movement/drug effects,genetics Cell Proliferation/drug effects Drug Resistance, Neoplasm/drug effects,genetics Hematologic Neoplasms/drug therapy,genetics,metabolism,pathology Hematopoiesis/drug effects,genetics Humans Mutation/drug effects Oncogene Proteins/genetics,metabolism Signal Transduction/drug effects,genetics Transforming Growth Factor beta/genetics,metabolism
Chemicals
Oncogene Proteins Transforming Growth Factor beta
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Dong Mei
Department of Medicine, Duke University Medical Center, Box 2631, Durham, NC 27710, USA.
Blobe Gerard C
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Article Info
Journal
Blood
Abbr.
Blood
ISSN
0006-4971
DOI
10.1182/blood-2005-10-4169
Published
2006-06-15
Epub
2006-00-16
Pages
4589-96
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC1895802
Subset
IM
Grants
NCI NIH HHS · CA100065 · United States
NCI NIH HHS · CA105255 · United States
NCI NIH HHS · CA106307 · United States
External Links
PubMed source DOI: 10.1182/blood-2005-10-4169 PMC Full Text View journal details
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