Myelodysplastic syndrome

The role of TGFβ in hematopoiesis and myeloid disorders

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Abstract

The role of transforming growth factor-β (TGFβ) signaling in embryological development and tissue homeostasis has been thoroughly characterized. Its canonical downstream cascade is well known, even though its true complexity and other non-canonical pathways are still being explored. TGFβ signaling has been described as an important pathway involved in carcinogenesis and cancer progression. In the hematopoietic compartment, the TGFβ pathway is an important regulator of proliferation and differentiation of different cell types and has been implicated in the pathogenesis of a diverse variety of bone marrow disorders. Due to its importance in hematological diseases, novel inhibitors of this pathway are being developed against a number of hematopoietic disorders, including myelodysplastic syndromes (MDS). In this review, we provide an overview of the TGFβ pathway, focusing on its role in hematopoiesis and impact on myeloid disorders. We will discuss therapeutic interventions with promising results against MDS.

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Acknowledgements

This work is supported in part by the University of Texas MD Anderson Cancer Center Support Grant CA016672 and the University of Texas MD Anderson MDS/AML Moon Shot.

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Correspondence to Guillermo Garcia-Manero.

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GG-M declares support and an advisory role for Celgene Corporation and Acceleron Pharma. The remaining authors declare that they have no conflict of interest.

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