Lei Hu, Tu Yaoyao, Yang Li, Jin Jin, Luo Hao, Xu Hanzhang, Kang Jingwu, Zhou Li, Wu Yingli
a Faculty of Basic Medicine, Chemical Biology Division of Shanghai Universities E-Institutes, Hongqiao International Institute of Medicine, Shanghai Tongren Hospital, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao Tong University School of Medicine , Shanghai , China.
b State Key Laboratory of Bioorganic and Natural Products Chemistry, Chinese Academy of Sciences , Shanghai , China.
Cancer Invest. 2019;37(6):242-252. doi: 10.1080/07357907.2019.1630633. Epub 2019 Jul 11.
Drug resistance to TKIs and the existance of CML leukemia stem cells is an urgent problem. In this study, we demonstrate that quinacrine (QC) induces apoptosis in BCR-ABL positive CML and acute lymphoblastic leukemia (ALL) cells. Interestingly, QC inhibits the colony formation of primary CD34 progenitor/stem leukemia cells from CML patients. QC targets RNA polymerase I, which produces ribosomal (r)RNA, involving in protein translation process. Also, QC treatment prolongs CML-like mice survival and inhibits K562 tumor growth . In conclusion, we demonstrate that QC depletes BCR-ABL protein and suppresses Ph-positive leukemia cells and .
对酪氨酸激酶抑制剂（TKIs）的耐药性以及慢性粒细胞白血病（CML）白血病干细胞的存在是一个紧迫的问题。在本研究中，我们证明奎纳克林（QC）可诱导BCR-ABL阳性的CML和急性淋巴细胞白血病（ALL）细胞凋亡。有趣的是，QC抑制了来自CML患者的原代CD34祖细胞/白血病干细胞的集落形成。QC作用于RNA聚合酶I，该酶产生核糖体（r）RNA，参与蛋白质翻译过程。此外，QC治疗可延长CML样小鼠的生存期并抑制K562肿瘤生长。总之，我们证明QC可消耗BCR-ABL蛋白并抑制Ph阳性白血病细胞。
