title: Deregulation of mitochondrial ATPsyn-β in acute myeloid leukemia cells and with increased drug resistance.
abstract: The mechanisms underlying the development of multidrug resistance in acute myeloid leukemia are not fully understood. Here we analyzed the expressions of mitochondrial ATPsyn-β in adriamycin-resistant cell line HL-60/ADM and its parental cell line HL-60. Meanwhile we compared the differences of mitochondrial ATPsyn-β expression and ATP synthase activity in 110 acute myeloid leukemia (AML, non-M3) patients between relapsed/refractory and those in remission. Our results showed that down-regulation of ATPsyn-β expression by siRNA in HL-60 cells increased cell viability and apoptotic resistance to adriamycin, while up-regulation of mitochondrial ATPsyn-β in HL-60/ADM cells enhanced cell sensitivity to adriamycin and promoted apoptosis. Mitochondrial ATPsyn-β expression and ATP synthase activity in relapsed/refractory acute myeloid leukemia patients were downregulated. This downregulated ATPsyn-β expression exhibited a positive correlation with the response to adriamycin of primary cells. A lower expression of ATPsyn-β in newly diagnosed or relapsed/refractory patients was associated with a shorter first remission duration or overall survival. Our findings show mitochondrial ATPsyn-β plays an important role in the mechanism of multidrug resistance in AML thus may present both a new marker for prognosis assessment and a new target for reversing drug resistance.
authors.affiliation: Division of Hematology, Institution of Molecular Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Division of Hematology, Institution of Molecular Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
authors.forename: Jingke
authors.initials: J
authors.lastname: Yang
authors.affiliation: Division of Hematology, Institution of Molecular Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
authors.forename: Ruijuan
authors.initials: R
authors.lastname: Li
authors.affiliation: Division of Hematology, Institution of Molecular Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
authors.forename: Sufang
authors.initials: S
authors.lastname: Liu
authors.affiliation: Division of Hematology, Institution of Molecular Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
authors.forename: Yunxiao
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Division of Hematology, Institution of Molecular Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
authors.forename: Wenli
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Division of Hematology, Institution of Molecular Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yi
authors.affiliation: Division of Hematology, Institution of Molecular Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
authors.forename: Yunya
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Division of Hematology, Institution of Molecular Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
authors.forename: Fanjie
authors.initials: F
authors.lastname: Gong
authors.affiliation: Division of Hematology, Institution of Molecular Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
authors.forename: Honglin
authors.initials: H
authors.lastname: Peng
authors.affiliation: Division of Hematology, Institution of Molecular Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
authors.forename: Minfei
authors.initials: M
authors.lastname: Pei
authors.affiliation: Division of Hematology, Institution of Molecular Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
authors.forename: Mingyang
authors.initials: M
authors.lastname: Deng
authors.affiliation: Division of Hematology, Institution of Molecular Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
authors.forename: Guangsen
authors.initials: G
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D015536:Down-Regulation; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000235:genetics / Q000502:physiology; D019008:Drug Resistance, Neoplasm / Q000235:genetics / Q000502:physiology; D005260:Female; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000201:enzymology; D025261:Mitochondrial Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D055815:Young Adult
chemical_list: C506526:ATP5F1B protein, human; D000970:Antineoplastic Agents; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D004317:Doxorubicin; D025261:Mitochondrial Proton-Translocating ATPases