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

ABSTRACT: Altered transforming growth factor-beta (TGF-?) signaling has been implicated in the pathogenesis of leukemia. Although TGF-? type II receptor (T?RII) 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 T?RII isoforms (T?RII and T?RII-B) are abnormally expressed in leukemic cells, as compared to normal hematopoietic cells. T?RII-B, but not T?RII, was found to promote cell cycle arrest, apoptosis, and differentiation of leukemic cells. T?RII-B also enhanced TGF-?1 binding and downstream signaling and reduced tumorigenicity in vivo. By contrast, T?RII blocked all-trans retinoic acid-induced differentiation through inhibition of T?RII-B. Overall survival was significantly lower in acute myeloid leukemia (AML) patients with high compared to low T?RII expression. Thus, whereas T?RII-B is a potent inducer of cell cycle arrest, apoptosis, and differentiation, higher T?RII expression correlates with poor clinical prognosis in AML.

SUBMITTER: Wu Y 

PROVIDER: S-EPMC5354639 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature