Wu Shenghao, Zheng Cuiping, Chen Songyan, Lin Bijing, Chen Yuemiao, Zhou Wenjin, Li Zhenyu
Department of Hematology, The Dingli Clinical Institute of Wenzhou Medical University (Wenzhou Central Hospital), Wenzhou, Zhejiang 325000, China.
Department of Hematology, The Dingli Clinical Institute of Wenzhou Medical University (Wenzhou Central Hospital), Wenzhou, Zhejiang 325000, China.
Biochem Biophys Res Commun. 2015 Jan 2;456(1):367-72. doi: 10.1016/j.bbrc.2014.11.089. Epub 2014 Dec 2.
Adiponectin, a member of adipokines, is a functional ligand for Adiponectin Receptor-1 (AdipoR1) and Adiponectin Receptor-2 (AdipoR2), and has been found to be linked to the risk of CML. Imatinib has undoubtedly revolutionised the management and outcome of chronic myeloid leukemia (CML), however imatinib resistance has been recognized as a major problem in CML therapy. In this study, we first established imatinib-resistant K562 CML cells, and then evaluated the effect of Adiponectin in reversing imatinib resistance. The data presented here demonstrated that Adiponectin was able to reverse K562 resistance to imatinib in vitro and in vivo. Additional data with molecular approaches suggested that the reversion of Adiponectin in imatinib resistance signals through AdipoR1 but not AdipoR2 to downregulate Bcr-Abl expression and effect in imatinib-resistant K562 CML cells. Taken together, our data showed that Adiponectin can reverse imatinib resistance in CML, and to a certain extent elucidate the mechanism of Adiponectin reversing imatinib resistance that may provide a new and promising approach in imatinib resistance management in CML therapy.
脂联素是脂肪因子的一种，是脂联素受体1（AdipoR1）和脂联素受体2（AdipoR2）的功能性配体，并且已发现其与慢性粒细胞白血病（CML）的风险相关。伊马替尼无疑彻底改变了慢性髓性白血病（CML）的治疗和预后，然而伊马替尼耐药已被认为是CML治疗中的一个主要问题。在本研究中，我们首先建立了伊马替尼耐药的K562 CML细胞，然后评估脂联素在逆转伊马替尼耐药方面的作用。此处呈现的数据表明，脂联素在体外和体内均能够逆转K562对伊马替尼的耐药性。分子方法的其他数据表明，脂联素在伊马替尼耐药信号中的逆转作用是通过AdipoR1而非AdipoR2来下调Bcr-Abl表达，并在伊马替尼耐药的K562 CML细胞中发挥作用。综上所述，我们的数据表明脂联素可以逆转CML中的伊马替尼耐药性，并在一定程度上阐明了脂联素逆转伊马替尼耐药性的机制，这可能为CML治疗中伊马替尼耐药的管理提供一种新的、有前景的方法。
