Oncotarget

Research Papers:

Abnormal expression of TGF-beta type II receptor isoforms contributes to acute myeloid leukemia

Yong Wu, Min Su, ShuX Zhang, Yu Cheng, Xiao Y. Liao, Bao Y. Lin and Yuan Z. Chen _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2017; 8:10037-10049. https://doi.org/10.18632/oncotarget.14325

Metrics: PDF 1490 views  |   HTML 2033 views  |   ?  


Abstract

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

Correspondence to:

Yuanzhong Chen, email: chenyz@mail.fjmu.edu.cn

Keywords: TGF-β, type II receptor, isoform, myeloid, leukemia

Received: April 14, 2016    Accepted: November 30, 2016    Published: December 28, 2016

ABSTRACT

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 14325