title: Adiponectin signals through Adiponectin Receptor 1 to reverse imatinib resistance in K562 human chronic myeloid leukemia cells.
abstract: 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.
authors.affiliation: Department of Hematology, The Dingli Clinical Institute of Wenzhou Medical University (Wenzhou Central Hospital), Wenzhou, Zhejiang 325000, China. Electronic address: shenghao_wu@126.com.
authors.forename: Shenghao
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Hematology, The Dingli Clinical Institute of Wenzhou Medical University (Wenzhou Central Hospital), Wenzhou, Zhejiang 325000, China.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Department of Hematology, The Dingli Clinical Institute of Wenzhou Medical University (Wenzhou Central Hospital), Wenzhou, Zhejiang 325000, China.
authors.forename: Songyan
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Hematology, The Dingli Clinical Institute of Wenzhou Medical University (Wenzhou Central Hospital), Wenzhou, Zhejiang 325000, China.
authors.forename: Bijing
authors.initials: B
authors.lastname: Lin
authors.affiliation: Department of Hematology, The Dingli Clinical Institute of Wenzhou Medical University (Wenzhou Central Hospital), Wenzhou, Zhejiang 325000, China.
authors.forename: Yuemiao
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Hematology, The Dingli Clinical Institute of Wenzhou Medical University (Wenzhou Central Hospital), Wenzhou, Zhejiang 325000, China.
authors.forename: Wenjin
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221000, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Li
mesh_terms: D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides / Q000627:therapeutic use*; D002453:Cell Cycle; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000068877:Imatinib Mesylate; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use*; D034741:RNA, Small Interfering / Q000378:metabolism; D054419:Receptors, Adiponectin / Q000378:metabolism*; D013997:Time Factors
chemical_list: C475418:ADIPOR1 protein, human; D052242:Adiponectin; D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D034741:RNA, Small Interfering; D054419:Receptors, Adiponectin; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl
keywords: Adiponectin; Adiponectin Receptor; Bcr-Abl; Chronic myeloid leukemia; Imatinib; Resistance