Redox-dependent protein S-glutathionylation governs azacitidine sensitivity and resistance in AML

Hypomethylation therapy significantly prolongs survival of patients with high-risk myelodysplastic syndrome progressing to acute myeloid leukaemia, yet most patients develop resistance. In this work we identified redox-regulated mechanisms of hypomethylation therapy and revealed that in resistant cells, hypomethylation therapy is failing to induce oxidative modifications of proteins. Modulation of redox homeostasis by targeting glutathione metabolism induces protein oxidation in resistant cells and overcomes chemoresistance.