
급성 골수성 백혈병 세포에서 미토콘드리아 전사 억제가 BCL-2 억제제에 대한 감수성을 증가시킨다.


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Overcoming drug-resistance and the subsequent relapse that often occurs with monotherapy is crucial in the treatment of acute myeloid leukemia. We here demonstrate that therapy-resistant leukemia initiating cells can be targeted using a novel inhibitor of mitochondrial transcription (IMT). The compound inhibits mitochondrial RNA polymerase activity and sensitizes the resistant population to the induction of apoptosis. In vitro studies on acute myeloid leukemia cells demonstrate that IMT prevents cell proliferation, and together with a selective BCL-2 inhibitor, venetoclax, induces apoptosis and suppress oxidative phosphorylation (OXPHOS) synergistically. AML mouse models treated with IMT in combination with venetoclax show prolonged survival in venetoclax-resistant models. Our findings suggest that certain therapy-resistant leukemia cell populations display a unique dependency on mitochondrial transcription and can be targeted with IMT.

### Competing Interest Statement

CMG is a scientific co-founder of Pretzel Therapeutics Inc. Together with RD, TB, AU, PN, BMK who are employees of LDC, CMG is also co-inventor of the patent application WO 2019/057821. Medicinal chemistry and pharmacology part of this work was financed by the Max-Planck Gesellschaft e.V. under the framework agreement between Max-Planck and LDC.

Reduced mitochondrial transcription sensitizes acute myeloid leukemia cells to BCL-2 inhibition

급성-골수성-백혈병-세포에-대한-미토콘드리아-전사-감소의-bcl-2-억제제-감수성-증가-효과


급성 골수성 백혈병 세포에 대한 미토콘드리아 전사 감소의 BCL-2 억제제 감수성 증가 효과
