| http://purl.uniprot.org/citations/29431698 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/29431698 | http://www.w3.org/2000/01/rdf-schema#comment | "In acute myeloid leukemia (AML), chemotherapy resistance remains prevalent and poorly understood. Using functional proteomics of patient AML specimens, we identified MEF2C S222 phosphorylation as a specific marker of primary chemoresistance. We found that Mef2cS222A/S222A knock-in mutant mice engineered to block MEF2C phosphorylation exhibited normal hematopoiesis, but were resistant to leukemogenesis induced by MLL-AF9 MEF2C phosphorylation was required for leukemia stem cell maintenance and induced by MARK kinases in cells. Treatment with the selective MARK/SIK inhibitor MRT199665 caused apoptosis and conferred chemosensitivity in MEF2C-activated human AML cell lines and primary patient specimens, but not those lacking MEF2C phosphorylation. These findings identify kinase-dependent dysregulation of transcription factor control as a determinant of therapy response in AML, with immediate potential for improved diagnosis and therapy for this disease.Significance: Functional proteomics identifies phosphorylation of MEF2C in the majority of primary chemotherapy-resistant AML. Kinase-dependent dysregulation of this transcription factor confers susceptibility to MARK/SIK kinase inhibition in preclinical models, substantiating its clinical investigation for improved diagnosis and therapy of AML. Cancer Discov; 8(4); 478-97. ©2018 AACR.This article is highlighted in the In This Issue feature, p. 371."xsd:string |
| http://purl.uniprot.org/citations/29431698 | http://purl.org/dc/terms/identifier | "doi:10.1158/2159-8290.cd-17-1271"xsd:string |
| http://purl.uniprot.org/citations/29431698 | http://purl.uniprot.org/core/author | "Hebert J."xsd:string |
| http://purl.uniprot.org/citations/29431698 | http://purl.uniprot.org/core/author | "Letai A."xsd:string |
| http://purl.uniprot.org/citations/29431698 | http://purl.uniprot.org/core/author | "Ficarro S.B."xsd:string |
| http://purl.uniprot.org/citations/29431698 | http://purl.uniprot.org/core/author | "Levine R."xsd:string |
| http://purl.uniprot.org/citations/29431698 | http://purl.uniprot.org/core/author | "Armstrong S.A."xsd:string |
| http://purl.uniprot.org/citations/29431698 | http://purl.uniprot.org/core/author | "Marto J.A."xsd:string |
| http://purl.uniprot.org/citations/29431698 | http://purl.uniprot.org/core/author | "Takao S."xsd:string |
| http://purl.uniprot.org/citations/29431698 | http://purl.uniprot.org/core/author | "Spitzer B."xsd:string |
| http://purl.uniprot.org/citations/29431698 | http://purl.uniprot.org/core/author | "Melnick A."xsd:string |
| http://purl.uniprot.org/citations/29431698 | http://purl.uniprot.org/core/author | "Sauvageau G."xsd:string |
| http://purl.uniprot.org/citations/29431698 | http://purl.uniprot.org/core/author | "Kentsis A."xsd:string |
| http://purl.uniprot.org/citations/29431698 | http://purl.uniprot.org/core/author | "Gunasekera S."xsd:string |
| http://purl.uniprot.org/citations/29431698 | http://purl.uniprot.org/core/author | "Brown F.C."xsd:string |
| http://purl.uniprot.org/citations/29431698 | http://purl.uniprot.org/core/author | "Reed C."xsd:string |
| http://purl.uniprot.org/citations/29431698 | http://purl.uniprot.org/core/author | "de Stanchina E."xsd:string |
| http://purl.uniprot.org/citations/29431698 | http://purl.uniprot.org/core/author | "Mark W."xsd:string |
| http://purl.uniprot.org/citations/29431698 | http://purl.uniprot.org/core/author | "Romanienko P."xsd:string |
| http://purl.uniprot.org/citations/29431698 | http://purl.uniprot.org/core/author | "O'Donnell C."xsd:string |
| http://purl.uniprot.org/citations/29431698 | http://purl.uniprot.org/core/author | "Tallman M.S."xsd:string |
| http://purl.uniprot.org/citations/29431698 | http://purl.uniprot.org/core/author | "Krivtsov A.V."xsd:string |
| http://purl.uniprot.org/citations/29431698 | http://purl.uniprot.org/core/author | "Gonen M."xsd:string |
| http://purl.uniprot.org/citations/29431698 | http://purl.uniprot.org/core/author | "Still E."xsd:string |