Reversing the Warburg Effect: YW3-56 Induces Leukemia Differentiation via AKT-Mediated Glucose Metabolic Reprogramming.

ABSTRACT: Background: Protein arginine deiminase 4 (PAD4) has emerged as a promising therapeutic target for acute promyelocytic leukemia (APL) because of its role in epigenetic regulation and leukemogenesis. All-trans retinoic acid, a standard differentiation agent in APL therapy, has been shown to upregulate PAD4 expression during leukemic cell maturation. Interestingly, first-generation PAD4 inhibitors also promote differentiation, but simultaneously trigger compensatory PAD4 overexpression, underscoring the unresolved complexity of PAD4 modulation in leukemia therapy. Methods: In this study, we employed mass cytometry and transcriptomic-proteomic integrated analysis to investigate the underlying mechanisms of YW3-56, a dual-function PAD4 inhibitor against protein expression and enzy

SUBMITTER: Zhu D 

PROVIDER: S-EPMC12655338 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature