Nucleophosmin 1: from its pathogenic role to a tantalizing therapeutic target in acute myeloid leukemia

ABSTRACT

Nucleophosmin 1 (NPM1, also known as B23) is a multifunctional protein involved in a variety of cellular processes, including ribosomal maturation, centrosome replication, maintenance of genomic stability, cell cycle control, and apoptosis. NPM1 is the most commonly mutated gene in adult acute myeloid leukemia (AML) and is present in approximately 40% of all AML cases. The underlying mechanisms of mutant NPM1 (NPM1^mut) in leukemogenesis remain unclear. This review summarizes the structure and physiological function of NPM1, mechanisms underlying the pathogenesis of NPM1-mutated AML, and the potential role of NPM1 as a therapeutic target. It is reported that dysfunctional NPM1 might cause AML pathogenesis via its role as a protein chaperone, inhibiting differentiation of leukemia stem cells and regulation of non-coding RNAs. Besides conventional chemotherapies, NPM1 is a promising therapeutic target against AML that warrants further investigation. NPM1-based therapeutic strategies include inducing nucleolar relocalisation of NPM1 mutants, interfering with NPM1 oligomerization, and NPM1 as an immune response target.

KEYWORDS:

• Acute myeloid leukemia
• nucleophosmin 1
• somatic mutation
• leukemic pathogenesis
• therapeutic target

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Additional information

Funding

This study was funded by the Huai’an City Health Scientific Research Project [grant number: HAWJ202109] and the development fund of Xuzhou Medical University [grant number: XYFM2021036].