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Tytuł:
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Combinatorial Genetics Uncovers Novel Targets for the Treatment of Npm1/Cohesin Mutated AML
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Autorzy:
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Meyer, Alison E
Stelloh, Cary
Fisher, Joseph B
Pulakanti, Kirthi
Vassiliou, George S.
Viny, Aaron D
Levine, Ross L.
Rao, Sridhar
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Źródło:
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Blood; November 2018, Vol. 132 Issue: 1, Number 1 Supplement 1 p2598-2598, 1p
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Current precision medicine approaches typically target a single genetic mutation. However, adult acute myeloid leukemia (AML) is difficult to treat due to its genetic complexity. Approximately 30 somatic mutations have been found to be recurrent, with an average of 5-15 mutations present per patient (Cancer Genome Atlas 2013). Therefore, combinatorial genetic approaches have the power to uncover novel gene targets that can be used to tailor therapies to an individual's unique mutational spectrum. Mutations in NPM1commonly occur in in AML. Approximately 25-30% of patients harbor a specific variant of the NPM1mutation referred to as NPM1cA, which results in mislocalization of the Npm1 protein from the nucleus to the cytoplasm (Cancer Genome Atlas 2013; Falini 2005). While NPM1cAis considered to be a driver of AML development, mice with this mutation develop AML with a long latency (18 months) and with incomplete penetrance (Vassiliou 2011). In addition, those mice that do develop AML acquire additional genetic mutations, suggesting that NPM1cAcooperates with serially acquired mutations to drive AML development (Dovey 2017).