Quinacrine Depletes BCR-ABL and Suppresses Ph-Positive Leukemia Cells
Quinacrine Depletes BCR-ABL and Suppresses Ph-Positive Leukemia Cells
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奎纳克林消耗 BCR-ABL 并抑制 Ph 阳性白血病细胞
DOI：
10.1080/07357907.2019.1630633
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发表时间：
2019
影响因子：
2.4
通讯作者：
Wu Yingli
中科院分区：
文献类型：
--
作者：
Lei Hu;Tu Yaoyao;Yang Li;Jin Jin;Luo Hao;Xu Hanzhang;Kang Jingwu;Zhou Li;Wu Yingli
摘要TKI耐药和CML白血病干细胞的存在是一个亟待解决的问题。在这项研究中，我们证明奎纳克林（QC）诱导BCR-ABL阳性CML和急性淋巴细胞白血病（ALL）细胞凋亡。有趣的是，QC抑制来自CML患者的原代CD 34+祖细胞/干细胞白血病细胞殖民地形成。QC靶向RNA聚合酶I，其产生核糖体（r）RNA，参与蛋白质翻译过程。此外，QC处理降低CML样小鼠的存活率并抑制体内K562肿瘤生长。总之，我们证明，QC耗尽BCR-ABL蛋白和抑制Ph阳性白血病细胞在体外和体内。
Abstract 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 vivo. In conclusion, we demonstrate that QC depletes BCR-ABL protein and suppresses Ph-positive leukemia cells in vitro and in vivo.