Perturbing LSD1 and WNT rewires transcription to synergistically induce AML differentiation.

ABSTRACT: Impaired differentiation is a hallmark of myeloid malignancies^1,2. Therapies that enable cells to circumvent the differentiation block, such as all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), are by and large curative in acute promyelocytic leukaemia³, but whether 'differentiation therapy' is a generalizable therapeutic approach for acute myeloid leukaemia (AML) and beyond remains incompletely understood. Here we demonstrate that simultaneous inhibition of the histone demethylase LSD1 (LSD1i) and the WNT pathway antagonist GSK3 kinase⁴ (GSK3i) robustly promotes therapeutic differentiation of established AML cell lines and primary human AML cells, as well as reducing tumour burden and significantly extending survival in a patient-derived xenograft

SUBMITTER: Hosseini A 

PROVIDER: S-EPMC12158781 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature