1. Nucleophosmin 1 Mutations in Acute Myeloid Leukemia
- Author
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Ghayas C. Issa, Nicholas J. Short, Jabra Zarka, and Rashmi Kanagal-Shamanna
- Subjects
0301 basic medicine ,NPM1 ,Cytoplasm ,lcsh:QH426-470 ,Ribosome biogenesis ,Review ,Biology ,03 medical and health sciences ,0302 clinical medicine ,AML ,hemic and lymphatic diseases ,Gene expression ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Gene ,Genetics (clinical) ,Nucleophosmin ,Myeloid leukemia ,Nuclear Proteins ,nucleophosmin (NPM1) ,medicine.disease ,targeted therapies ,Leukemia ,Leukemia, Myeloid, Acute ,lcsh:Genetics ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Mutation ,Cancer research ,gene expression ,ADP-Ribosylation Factor 1 ,Bone marrow ,Tumor Suppressor Protein p53 - Abstract
Nucleophosmin (NPM1) is a ubiquitously expressed nucleolar protein involved in ribosome biogenesis, the maintenance of genomic integrity and the regulation of the ARF-p53 tumor-suppressor pathway among multiple other functions. Mutations in the corresponding gene cause a cytoplasmic dislocation of the NPM1 protein. These mutations are unique to acute myeloid leukemia (AML), a disease characterized by clonal expansion, impaired differentiation and the proliferation of myeloid cells in the bone marrow. Despite our improved understanding of NPM1 mutations and their consequences, the underlying leukemia pathogenesis is still unclear. Recent studies that focused on dysregulated gene expression in AML with mutated NPM1 have shed more light into these mechanisms. In this article, we review the current evidence on normal functions of NPM1 and aberrant functioning in AML, and highlight investigational strategies targeting these mutations.
- Published
- 2020