icnv_a_1630633_sm7370.pdf (267.56 kB)
0/0

Quinacrine Depletes BCR-ABL and Suppresses Ph-Positive Leukemia Cells

Download (267.56 kB)
journal contribution
posted on 12.07.2019 by Hu Lei, Yaoyao Tu, Li Yang, Jin Jin, Hao Luo, Hanzhang Xu, Jingwu Kang, Li Zhou, Yingli Wu

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.

Funding

This work was supported in part by grants from the National Key Research and Development Program of China (No. 2017YFA0505202), the National Natural Science Foundation of China (81570112, 81570118,81700475), State Key Laboratory of Bioorganic and Natural Produces Chemistry, State Key Laboratory of Phytochemistry and Plant Resources in West China (No. P2015-KF05).

History

Licence

Exports