Abnormal expression of TGF-beta type II receptor isoforms contributes to acute myeloid leukemia
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Yong Wu1, Min Su1, ShuX Zhang1, Yu Cheng1, Xiao Y. Liao1, Bao Y. Lin1, Yuan Z. Chen1
1Fujian Institute of Hematology, Department of Hematology, Union Hospital, Fujian Medical University, Fuzhou, China
Yuanzhong Chen, email: email@example.com
Keywords: TGF-β, type II receptor, isoform, myeloid, leukemia
Received: April 14, 2016 Accepted: November 30, 2016 Published: December 28, 2016
Altered transforming growth factor-beta (TGF-β) signaling has been implicated in the pathogenesis of leukemia. Although TGF-β type II receptor (TβRII) isoforms have been isolated from human leukemia cells, their expression patterns and functions of these variants are unclear. In this study, we determined that two TβRII isoforms (TβRII and TβRII-B) are abnormally expressed in leukemic cells, as compared to normal hematopoietic cells. TβRII-B, but not TβRII, was found to promote cell cycle arrest, apoptosis, and differentiation of leukemic cells. TβRII-B also enhanced TGF-β1 binding and downstream signaling and reduced tumorigenicity in vivo. By contrast, TβRII blocked all-trans retinoic acid-induced differentiation through inhibition of TβRII-B. Overall survival was significantly lower in acute myeloid leukemia (AML) patients with high compared to low TβRII expression. Thus, whereas TβRII-B is a potent inducer of cell cycle arrest, apoptosis, and differentiation, higher TβRII expression correlates with poor clinical prognosis in AML.
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