Quinacrine Depletes BCR-ABL and Suppresses Ph-Positive Leukemia Cells.
Hu LeiYaoyao TuLi YangJin JinHao LuoHan-Zhang XuJingwu KangLi ZhouYingli WuPublished in: Cancer investigation (2019)
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.
Keyphrases
- chronic myeloid leukemia
- acute lymphoblastic leukemia
- induced apoptosis
- tyrosine kinase
- stem cells
- acute myeloid leukemia
- cell cycle arrest
- bone marrow
- signaling pathway
- end stage renal disease
- metabolic syndrome
- adipose tissue
- protein protein
- insulin resistance
- mesenchymal stem cells
- cell therapy
- smoking cessation