Transforming Growth Factor Signaling Pathway

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Blood First Edition Paper, prepublished online February 16, 2006; DOI

10.1182/blood-2005-10-4169. This Article

Submitted October 20, 2005

Accepted February 3, 2006

Role of transforming growth factor- in hematological malignancies

Mei Dong and Gerard C Blobe*

Departments of Medicine and Pharmacology and Cancer Biology, Duke

University Medical Center, Durham, NC, USA

* Corresponding author; email: blobe001@....

The transforming growth factor- (TGF-) signaling pathway is an

essential regulator of cellular processes including proliferation,

differentiation, migration and cell survival. During hematopoiesis,

the TGF- signaling pathway is a potent negative regulator of

proliferation, while stimulating differentiation and apoptosis when

appropriate. In hematological malignancies, including leukemias,

myeloproliferative disorders, lymphomas and multiple myeloma,

resistance to these homeostatic effects of TGF- develops. Mechanisms

for this resistance include mutation or deletion of members of the

TGF- signaling pathway and disruption of the pathway by oncoproteins.

These alterations define a tumor suppressor role for the TGF- pathway

in human hematological malignancies. On the other hand, elevated

levels of TGF- can promote myelofibrosis and the pathogenesis of some

hematological malignancies through their effects on the stroma and

immune system. Advances in the TGF- signaling field should enable

targeting of the TGF- signaling pathway for the treatment of

hematological malignancies.