Beyond FOXO1: AS1842856 inhibits GSK3 to enhance cytotoxic effects in B-ALL.

ABSTRACT:

Abstract

Activation of the transcription factor forkhead box O1 (FOXO1) contributes to multiple pathological processes. The FOXO1 inhibitor AS1842856 demonstrated strong therapeutic effects in preclinical models of common diseases such as diabetes and anthracycline-induced heart failure. We have previously identified FOXO1 as a B-cell acute lymphoblastic leukemia (B-ALL) dependency and demonstrated in in vivo B-ALL models that AS1842856 increased the survival of animals and decreased B-ALL tumor load in all critical organ compartments, but most efficiently in the central nervous system. Here, we interrogated the underlying molecular mechanisms by comparison of the transcriptomic effects of AS1842856 and Foxo1 knockout (Foxo1-KO) in a B-ALL mouse model. Despite the significant simil

SUBMITTER: Ketzer F 

PROVIDER: S-EPMC12274837 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature