Towards repositioning of quinacrine for treatment of acute myeloid leukemia - Promising synergies and in vivo effects

Leukemia Research
Anna ErikssonRolf Larsson

Abstract

We previously reported that the anti-malarial drug quinacrine has potential to be repositioned for treatment of acute myeloid leukemia (AML). As a next step towards clinical use, we assessed the efficacy of quinacrine in an AML-PS mouse model and investigated possible synergistic effects when combining quinacrine with nine other antileukemic compounds in two AML cell lines. Furthermore, we explored the in vivo activity of quinacrine in combination with the widely used AML agent cytarabine. The in vivo use of quinacrine (100mg/kg three times per week for two consecutive weeks) significantly suppressed circulating blast cells at days 30/31 and increased the median survival time (MST). The in vitro drug combination analysis yielded promising synergistic interactions when combining quinacrine with cytarabine, azacitidine and geldanamycin. Finally, combining quinacrine with cytarabine in vivo showed a significant decrease in circulating leukemic blast cells and increased MST compared to the effect of either drug used alone, thus supporting the findings from the in vitro combination experiments. Taken together, the repositioning potential of quinacrine for treatment of AML is reinforced by demonstrating significant in vivo activity a...Continue Reading

Citations

Mar 22, 2019·The Cancer Journal·Stefania OrecchioniFrancesco Bertolini
Feb 20, 2020·Cancers·Anna V WojcickiKathleen M Sakamoto
Sep 29, 2019·Seminars in Cancer Biology·Derek B OienViji Shridhar
Dec 20, 2020·International Journal of Biological Macromolecules·Samar M EtmanOssama Y Abdallah
Jul 24, 2020·Anti-cancer Agents in Medicinal Chemistry·Biswajit Das, Chanakya N Kundu

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