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- W3038382610 endingPage "1721" @default.
- W3038382610 startingPage "1707" @default.
- W3038382610 abstract "Abstract The nucleophosmin (NPM1) gene encodes for a multifunctional protein with prominent nucleolar localization that shuttles between nucleus and cytoplasm. NPM1 mutations represent the most common genetic lesion in adult acute myeloid leukemia (AML; about one third of cases), and they act deterministically to cause the aberrant cytoplasmic delocalization of NPM1 mutants. Because of its unique features, NPM1-mutated AML is recognized as a distinct entity in the 2017 World Health Organization (WHO) classification of hematopoietic neoplasms. Here, we focus on recently identified functions of wild-type NPM1 in the nucleolus and address new biological and clinical issues related to NPM1-mutated AML. The relevance of the cooperation between NPM1 and other mutations in driving AML with different outcomes is presented. We also discuss the importance of eradicating NPM1-mutated clones to achieve AML cure and the impact of preleukemic clonal hematopoiesis persistence in predisposing to second AML. The contribution of HOX genes’ expression to the development of NPM1-mutated AML is also highlighted. Clinically, yet unsolved diagnostic issues in the 2017 WHO classification of myeloid neoplasms and the importance of NPM1 mutations in defining the framework of European LeukemiaNet genetic-based risk stratification are discussed. Finally, we address the value and limits of NPM1-based measurable residual disease assessment for treatment guidance and present the results of promising preclinical studies with XPO1 and menin-MLL inhibitors." @default.
- W3038382610 created "2020-07-10" @default.
- W3038382610 creator A5008077055 @default.
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- W3038382610 creator A5076644963 @default.
- W3038382610 creator A5084332214 @default.
- W3038382610 date "2020-10-08" @default.
- W3038382610 modified "2023-10-11" @default.
- W3038382610 title "NPM1-mutated acute myeloid leukemia: from bench to bedside" @default.
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