Leukemia Cell of Origin Influences Apoptotic Priming and Sensitivity to LSD1 Inhibition

白血病细胞来源影响细胞凋亡启动和对 LSD1 抑制的敏感性

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作者:Sheng F Cai, S Haihua Chu, Aaron D Goldberg, Salma Parvin, Richard P Koche, Jacob L Glass, Eytan M Stein, Martin S Tallman, Filiz Sen, Christopher A Famulare, Monica Cusan, Chun-Hao Huang, Chun-Wei Chen, Lihua Zou, Keith B Cordner, Nicole L DelGaudio, Vidushi Durani, Mitali Kini, Madison Rex, Helen

Significance

We demonstrate that the cell of origin of leukemia initiation influences p53 activity and dictates therapeutic sensitivity to pharmacologic LSD1 inhibitors via the transcription factor EVI1. We show that drug resistance could be overcome in HSC-derived leukemias by combining LSD1 inhibition with venetoclax.See related commentary by Gu et al., p. 1445.This article is highlighted in the In This Issue feature, p. 1426.

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