Lysosome Inhibition by Mefloquine Preferentially Enhances the Cytotoxic Effects of Tyrosine Kinase Inhibitors in Blast Phase Chronic Myeloid Leukemia.

ABSTRACT: Despite the efficacy of BCR-ABL tyrosine kinase inhibitors (TKIs) in chronic phase-chronic myeloid leukemia, the management of blast phase-chronic myeloid leukemia (BP-CML) remains a challenge. Therefore, there is an urgent need to identify alternative agents that act synergistically with BCR-ABL TKIs in BP-CML. Our results show that the anti-malarial agent, mefloquine augments the efficacy of TKIs in CML cell lines and primary CML cells in vitro, including those with the T315I mutation. This effect is selective as mefloquine is more effective in inducing apoptosis, inhibiting colony formation and self-renewal capacity of CD34⁺ cells derived from TKI-resistant BP-CML patients than normal cord blood (CB) CD34⁺ stem/progenitor cells. Notably, the combination of mefloqui

SUBMITTER: Lam Yi H 

PROVIDER: S-EPMC6611990 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature