Knockdown of SOD1 sensitizes the CD34+ CML cells to imatinib therapy.
Leukemia stem cell is thought to be one of the leading causes of imatinib resistance and the resultant relapse of chronic myelogenous leukemia (CML). Eradicating the leukemia stem cells holds the promise of CML treatment. In this study, we found that the CD34+ subpopulation in the CML cell line K562 had a higher expression of SOD1 than that in the CD34 negative cells. Knockdown of SOD1 in CD34+ cells had no significant effects on cell survival and growth, while it sensitized the CD34+ cells to imatinib therapy. N-acetyl-L cysteine (NAC) blocked the pro-apoptotic effects of SOD1 knockdown, suggesting the antioxidant effects of SOD1 was essential for the resistance of CD34+ cells to imatinib therapy. In summary, our results suggest that antagonizing the enhanced endogenous antioxidant activity in leukemia stem cells sheds lights on CML therapy.
Liu
Li
L
Department of Hematology, Tangdu Hospital, Fourth Military Medical University, Baqiao District, Xinshi Road No1, Xi'an, 710038, China. liuli1@medmail.com.cn
Chen
Renan
R
Huang
Siyong
S
Wu
Yanlan
Y
Li
Guohui
G
Liu
Qiang
Q
Yin
Dandan
D
Liang
Yingmin
Y
D018952:Antigens, CD34 / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides; D015153:Blotting, Western; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D006801:Humans; D000068877:Imatinib Mesylate; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors*; D000072105:Superoxide Dismutase-1; D014162:Transfection
D018952:Antigens, CD34; D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C000606290:SOD1 protein, human; D000068877:Imatinib Mesylate; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
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