{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T01:51:22Z","timestamp":1778550682882,"version":"3.51.4"},"reference-count":27,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,11,16]],"date-time":"2016-11-16T00:00:00Z","timestamp":1479254400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biology International"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Imatinib mesylate (IM) and other BCR\u2010ABL tyrosine kinase inhibitors (TKIs) have improved chronic myeloid leukemia (CML) patient survival markedly but fail to eradicate quiescent CML leukemia stem cells (LSCs). Thus, strategies targeting LSCs are required to induce long\u2010term remission and achieve cure. Here, we investigated the ability of topoisomerase II (Top II) inhibitor etoposide (Eto) to target CML LSCs. Treatment with Eto combined with IM markedly induced apoptosis in primitive CML CD34<jats:sup>+<\/jats:sup>CD38<jats:sup>\u2212<\/jats:sup>stem cells resistant to eradication by IM alone, but not in normal hematopoietic stem cells, CML and normal mature CD34<jats:sup>\u2212<\/jats:sup>cells, and other leukemia and lymphoma cell lines. The interaction of IM and Eto significantly inhibited phosphorylation of PDK1, AKT, GSK3, S6, and ERK proteins; increased the expression of pro\u2010apoptotic gene Bax; and decreased the expression of anti\u2010apoptotic gene c\u2010Myc in CML CD34<jats:sup>+<\/jats:sup>cells. Top II inhibitors treatment represents an attractive approach for targeting LSCs in CML patients undergoing TKIs monotherapy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cbin.10686","type":"journal-article","created":{"date-parts":[[2016,9,28]],"date-time":"2016-09-28T05:49:18Z","timestamp":1475041758000},"page":"16-23","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Selective and effective targeting of chronic myeloid leukemia stem cells by topoisomerase II inhibitor etoposide in combination with imatinib mesylate in vitro"],"prefix":"10.1002","volume":"41","author":[{"given":"Man\u2010Yu","family":"Liu","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences Southern Medical University Guangzhou P. R. China"},{"name":"Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances Guangdong Pharmaceutical University Guangzhou Higher Education Mega Center Guangzhou 510006 P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei\u2010Zhang","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances Guangdong Pharmaceutical University Guangzhou Higher Education Mega Center Guangzhou 510006 P. R. China"},{"name":"Department of Biochemistry and Molecular Biology School of Basic Courses, Guangdong Pharmaceutical University Guangzhou P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fen\u2010Fang","family":"Liao","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances Guangdong Pharmaceutical University Guangzhou Higher Education Mega Center Guangzhou 510006 P. R. China"},{"name":"Department of Biochemistry and Molecular Biology School of Basic Courses, Guangdong Pharmaceutical University Guangzhou P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing\u2010Qing","family":"Wu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances Guangdong Pharmaceutical University Guangzhou Higher Education Mega Center Guangzhou 510006 P. R. China"},{"name":"Department of Biochemistry and Molecular Biology School of Basic Courses, Guangdong Pharmaceutical University Guangzhou P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang\u2010Hua","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sun Yat\u2010Sen Memorial Hospital, Sun Yat\u2010Sen University Guangzhou P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong\u2010Hen","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances Guangdong Pharmaceutical University Guangzhou Higher Education Mega Center Guangzhou 510006 P. R. China"},{"name":"Department of Biochemistry and Molecular Biology School of Basic Courses, Guangdong Pharmaceutical University Guangzhou P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Cheng","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances Guangdong Pharmaceutical University Guangzhou Higher Education Mega Center Guangzhou 510006 P. R. China"},{"name":"Department of Biochemistry and Molecular Biology School of Basic Courses, Guangdong Pharmaceutical University Guangzhou P. R. 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