ATM/G6PD-driven redox metabolism promotes FLT3 inhibitor resistance in acute myeloid leukemia

Activating mutations in FMS-like tyrosine kinase 3 (FLT3) are common in acute myeloid leukemia (AML) and drive leukemic cell growth and survival. Although FLT3 inhibitors have shown considerable promise for the treatment of AML, they ultimately fail to achieve long-term remissions as monotherapy. To...

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Veröffentlicht in:	Proceedings of the National Academy of Sciences - PNAS 2016-10, Vol.113 (43), p.E6669-E6678
Hauptverfasser:	Gregory, Mark A., D’Alessandro, Angelo, Alvarez-Calderon, Francesca, Kim, Jihye, Nemkov, Travis, Adane, Biniam, Rozhok, Andrii I., Kumar, Amit, Kumar, Vijay, Pollyea, Daniel A., Wempe, Michael F., Jordan, Craig T., Serkova, Natalie J., Choon Tan, Aik, Hansen, Kirk C., DeGregori, James
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Antineoplastic Agents - pharmacology Ataxia Telangiectasia Mutated Proteins - antagonists & inhibitors Ataxia Telangiectasia Mutated Proteins - genetics Ataxia Telangiectasia Mutated Proteins - metabolism Benzothiazoles - pharmacology Biological Sciences Cell growth Cell Line, Tumor Cell Survival - drug effects Drug Resistance, Neoplasm - genetics Drug Therapy, Combination Female fms-Like Tyrosine Kinase 3 - antagonists & inhibitors fms-Like Tyrosine Kinase 3 - genetics fms-Like Tyrosine Kinase 3 - metabolism Gene Expression Regulation, Leukemic Genetics Glucosephosphate Dehydrogenase - antagonists & inhibitors Glucosephosphate Dehydrogenase - genetics Glucosephosphate Dehydrogenase - metabolism Humans Hydrazines - pharmacology Kinases Leukemia Leukemia, Myeloid, Acute - drug therapy Leukemia, Myeloid, Acute - genetics Leukemia, Myeloid, Acute - mortality Leukemia, Myeloid, Acute - pathology Metabolism Mice, Inbred NOD Middle Aged Mutation Oxidation-Reduction Phenylurea Compounds - pharmacology PNAS Plus Protein Kinase Inhibitors - pharmacology RNA, Small Interfering - genetics RNA, Small Interfering - metabolism Signal Transduction Survival Analysis Xenograft Model Antitumor Assays
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