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- Title
Deregulation of Mitochondrial ATPsyn-β in Acute Myeloid Leukemia Cells and with Increased Drug Resistance.
- Authors
Xiao, Xiang; Yang, Jingke; Li, Ruijuan; Liu, Sufang; Xu, Yunxiao; Zheng, Wenli; Yi, Yan; Luo, Yunya; Gong, Fanjie; Peng, Honglin; Pei, Minfei; Deng, Mingyang; Zhang, Guangsen
- 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.
- Subjects
MITOCHONDRIA; ADENOSINE triphosphate; MYELOID leukemia; MULTIDRUG resistance; DOXORUBICIN; CELL lines; SMALL interfering RNA
- Publication
PLoS ONE, 2013, Vol 8, Issue 12, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0083610