Role of nucleophosmin in acute myeloid leukemia

Abstract

Nucleophosmin (NPM) is a nucleolar phosphoprotein implicated in the regulation of multiple cellular functions, which possesses both oncogenic and tumor-suppressor properties. Mutations of the NPM1 gene leading to the expression of a cytoplasmic mutant protein, NPMc+, are the most frequent genetic abnormalities found in acute myeloid leukemias. Acute myeloid leukemias with mutated NPM1 have distinct characteristics, including a significant association with a normal karyotype, involvement of different hematopoietic lineages, a specific gene-expression profile and clinically, a better response to induction therapy and a favorable prognosis. NPMc+ maintains the capacity of wild-type NPM to interact with a variety of cellular proteins, and impairs their activity by delocalizing them to the cytoplasm. In this review we summarize recent discoveries concerning NPM function, and discuss their possible impact on the pathogenesis of acute myeloid leukemias with mutated NPM1.

Keywords::

• acute myeloid leukemia
• chromosomal translocations
• normal karyotype
• NPM mutations
• nucleophosmin
• protein–protein interactions
• subcellular localization

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.