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|Gene Variant Descriptions||NPM1 exon12 mutations are found in AML with normal karyotype and predominantly result in a frameshift at the C-terminal, with mutation of either or both T288 and/or T290 and five new terminal residues, VSLRK. As these mutations result in the cytoplasmic location of Npm1 protein, they are also called NPM1c+ or NPMc+ (PMID: 15659725, PMID: 16076867) and are transforming in cell culture (PMID: 26884713).|
|Associated Drug Resistance|
|Molecular Profile||Protein Effect||Treatment Approaches|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|NPM1 exon12||acute myeloid leukemia||sensitive||Ixazomib + Vorinostat||Preclinical - Cell culture||Actionable||In a preclinical study, Ixazomib (MLN9708) and Zolinza (vorinostat) synergistically induced apoptosis in NPMc+ (due to NPM1 exon 12 mutations) acute myeloid leukemia cells in culture (PMID: 26634271).||26634271|
|NPM1 exon12||acute myeloid leukemia||sensitive||Deguelin||Preclinical||Actionable||In preclinical studies, deguelin treatment of an AML cell line harboring NPM1 exon12 mutation resulted in reduced levels of mutant Npm1 protein and induced differentiation of the cells (PMID: 25242579, PMID: 25348016).||25242579 25348016|
|NPM1 exon12||acute myeloid leukemia||predicted - sensitive||Ixazomib||Case Reports/Case Series||Actionable||In a clinical study, Ixazomib (MLN9708) treatment resulted in significantly reduced peripheral blast cells in a NPMc+ (due to NPM1 exon 12 mutations) acute myeloid leukemia (AML) patient, and demonstrated selective toxicity towards NPMc+ AML cell lines in culture (PMID: 26634271).||26634271|