Fidyt, KlaudynaPastorczak, AgataGoral, AgnieszkaSzczygiel, KacperFendler, WojciechMuchowicz, AngelikaBartlomiejczyk, Marcin AdamMadzio, JoannaCyran, JuliaGraczyk-Jarzynka, AgnieszkaJansen, EugenePatkowska, ElzbietaLech-Maranda, EwaPal, DeepaliBlair, HelenBurdzinska, AnnaPedzisz, PiotrGlodkowska-Mrowka, ElizaDemkow, UrszulaGawle-Krawczyk, KarolinaMatysiak, MichalWiniarska, MagdalenaJuszczynski, PrzemyslawMlynarski, WojciechHeidenreich, OlafGolab, JakubFirczuk, Malgorzata2019-03-222019-03-222019-03-121878-02613086128410.1002/1878-0261.12476http://hdl.handle.net/10029/622926B cell precursor acute lymphoblastic leukemia (BCP-ALL) is a genetically heterogeneous blood cancer characterized by abnormal expansion of immature B cells. Although intensive chemotherapy provides high cure rates in a majority of patients, subtypes harboring certain genetic lesions, such as MLL rearrangements or BCR-ABL1 fusion, remain clinically challenging, necessitating a search for other therapeutic approaches. Herein, we aimed to validate antioxidant enzymes of the thioredoxin system as potential therapeutic targets in BCP-ALL. We observed oxidative stress along with aberrant expression of the enzymes associated with the activity of thioredoxin antioxidant system in BCP-ALL cells. Moreover, we found that auranofin and adenanthin, inhibitors of the thioredoxin system antioxidant enzymes, effectively kill BCP-ALL cell lines and pediatric and adult BCP-ALL primary cells, including primary cells co-cultured with bone marrow-derived stem cells. Furthermore, auranofin delayed the progression of leukemia in MLL-rearranged patient-derived xenograft model and prolonged the survival of leukemic NSG mice. Our results unveil the thioredoxin system as a novel target for BCP-ALL therapy, and indicate that further studies assessing the anticancer efficacy of combinations of thioredoxin system inhibitors with conventional anti BCP-ALL drugs should be continued.enB-ALLBCP-ALLantioxidant enzymesleukemiaoxidative stressperoxiredoxinthioredoxinArticleMol Oncol 2019; 13(5):1180-95