2. Academic Validation
  3. Quinacrine Depletes BCR-ABL and Suppresses Ph-Positive Leukemia Cells

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

  • Cancer Invest. 2019;37(6):242-252. doi: 10.1080/07357907.2019.1630633.
Hu Lei 1,  Yaoyao Tu 1,  Li Yang 1,  Jin Jin 1,  Hao Luo 1,  Hanzhang Xu 1,  Jingwu Kang 2,  Li Zhou 3,  Yingli Wu 1
Affiliations

Affiliations

  • 1 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.
  • 2 b State Key Laboratory of Bioorganic and Natural Products Chemistry, Chinese Academy of Sciences , Shanghai , China.
  • 3 c Department of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , China.
PMID: 31296070 DOI: 10.1080/07357907.2019.1630633
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.

Keywords

BCR-ABL; CML; Quinacrine; RNA polymerase I.

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