Autocrine transforming growth factor-beta regulation of hematopoiesis: many outcomes that depend on the context

Oncogene. 2005 Aug 29;24(37):5751-63. doi: 10.1038/sj.onc.1208921.


Transforming growth factor-beta (TGF-beta) is a pleiotropic regulator of all stages of hematopoieis. The three mammalian isoforms (TGF-beta1, 2 and 3) have distinct but overlapping effects on hematopoiesis. Depending on the differentiation stage of the target cell, the local environment and the concentration and isoform of TGF-beta, in vivo or in vitro, TGF-beta can be pro- or antiproliferative, pro- or antiapoptotic, pro- or antidifferentiative and can inhibit or increase terminally differentiated cell function. TGF-beta is a major regulator of stem cell quiescence, at least in vitro. TGF-beta can act directly or indirectly through effects on the bone marrow microenvironment. In addition, paracrine and autocrine actions of TGF-beta have overlapping but distinct regulatory effects on hematopoietic stem/progenitor cells. Since TGF-beta can act in numerous steps in the hematopoietic cascade, loss of function mutations in hematopoeitic stem cells (HSC) have different effects on hematopoiesis than transient blockade of autocrine TGF-beta1. Transient neutralization of autocrine TGF-beta in HSC has therapeutic potential. In myeloid and erythroid leukemic cells, autocrine TGF-beta1 and/or its Smad signals controls the ability of these cells to respond to various differentiation inducers, suggesting that this pathway plays a role in determining the cell fate of leukemic cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Cell Proliferation
  • Cell Survival
  • DNA-Binding Proteins / physiology
  • Extracellular Signal-Regulated MAP Kinases / physiology
  • Hematopoiesis*
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / physiology
  • Humans
  • Leukemia, Erythroblastic, Acute / etiology
  • MAP Kinase Signaling System
  • Mice
  • Signal Transduction
  • Smad Proteins
  • Trans-Activators / physiology
  • Transforming Growth Factor beta / physiology*


  • DNA-Binding Proteins
  • Smad Proteins
  • Trans-Activators
  • Transforming Growth Factor beta
  • Extracellular Signal-Regulated MAP Kinases