Wu Yong, Su Min, Zhang ShuX, Cheng Yu, Liao Xiao Y, Lin Bao Y, Chen Yuan Z
Fujian Institute of Hematology, Department of Hematology, Union Hospital, Fujian Medical University, Fuzhou, China.
Oncotarget. 2017 Feb 7;8(6):10037-10049. doi: 10.18632/oncotarget.14325.
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.
转化生长因子-β（TGF-β）信号通路改变与白血病的发病机制有关。虽然已从人白血病细胞中分离出TGF-β II型受体（TβRII）异构体，但这些变体的表达模式和功能尚不清楚。在本研究中，我们确定与正常造血细胞相比，两种TβRII异构体（TβRII和TβRII-B）在白血病细胞中异常表达。发现TβRII-B而非TβRII可促进白血病细胞的细胞周期停滞、凋亡和分化。TβRII-B还增强了TGF-β1结合和下游信号传导，并降低了体内肿瘤发生能力。相比之下，TβRII通过抑制TβRII-B阻断全反式维甲酸诱导的分化。急性髓系白血病（AML）患者中，TβRII高表达者的总生存期显著低于低表达者。因此，虽然TβRII-B是细胞周期停滞、凋亡和分化的有效诱导剂，但TβRII高表达与AML患者不良临床预后相关。
