Reduced SMAD7 leads to overactivation of TGF-beta signaling in MDS that can be reversed by a specific inhibitor of TGF-beta receptor I kinase.

Journal article

Even though myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis, the molecular alterations that lead to marrow failure have not been well elucidated. We have previously shown that the myelosuppressive TGF-β pathway is constitutively activated in MDS progenitors. Because there is conflicting data about upregulation of extracellular TGF-β levels in MDS, we wanted to determine the molecular basis of TGF-β pathway overactivation and consequent hematopoietic suppression ...

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Authors: Zhou, L; McMahon, C; Bhagat, T; Alencar, C; Yu, Y

• Publication status: Published
• Journal: Cancer research
• Volume: 71
• Issue: 3
• Pages: 955-963
• Publication date: 2011-02-01
• DOI: 10.1158/0008-5472.can-10-2933
• EISSN: 1538-7445
• ISSN: 0008-5472
• Language: English
• Keywords: Signal Transduction; Receptors, Transforming Growth Factor beta; Quinolines; Myelodysplastic Syndromes; Protein-Serine-Threonine Kinases; Humans; K562 Cells; Hematopoietic Stem Cells; Protein Kinase Inhibitors; Pyrazoles; Transforming Growth Factor beta; Smad7 Protein; Hematopoiesis; Anemia