A novel LSD1 inhibitor T-3775440 induces transdifferentiation in AML cell lines
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We describe the anti-leukemic activity and mechanism of action of T-3775440, a novel irreversible LSD1 inhibitor. Cell growth analysis of leukemia cell lines revealed that acute erythroleukemia (AEL) and acute megakaryoblastic leukemia cells (AMKL) are highly sensitive to this compound. T-3775440 treatment enforced transdifferentiation-like phenotypic change from erythroid/megakaryocytic lineages into granulomonocytic lineage. Our findings provide the rationale for testing LSD1 inhibitors as potential treatments with a novel mechanism of action for AML, particularly AEL and AMKL. Total RNA obtained from cells treated with or without 100 nM of T-3775440 for 24 hours in vitro. Effects of T-3775440 on AML cells lines were compared that of DMSO-treated control.
