NPM1

Nucleophosmin 1 (NPM1) is a ubiquitously expressed nucleolar phosphoprotein in humans, encoded by the NPM1 gene. It is also known as B23 or NPM and is a member of the nucleoplasmin family. NPM1 functions as a multifunctional chaperone involved in ribosome biogenesis, chromatin remodeling, and nucleolar organization, and it participates in cell cycle control and centrosome duplication. The protein shuttles between the nucleolus, nucleus, and cytoplasm, reflecting its dynamic roles in cellular homeostasis.

Structurally, NPM1 forms pentamers through its N-terminal oligomerization domain and contains an acidic C-terminal region with signals for nucleolar localization and, in mutated forms, a nuclear export signal. This structure underpins its interactions with ribosomal proteins, histones, and various nucleolar factors. Through these interactions, NPM1 contributes to pre-rRNA processing, ribosome assembly, and histone chaperoning, and it participates in pathways linked to the p53 tumor suppressor axis, notably via interactions with ARF (p14ARF).

NPM1 has particular clinical significance in acute myeloid leukemia (AML). The NPM1 gene is located on chromosome 5q35. Mutations in NPM1, most commonly a four-base insertion in exon 12, create a novel C-terminal nuclear export signal that causes cytoplasmic accumulation of NPM1 (NPM1c). This mutation defines a distinct AML subset; when occurring without concurrent FLT3-ITD mutations, it is associated with a relatively favorable prognosis and has diagnostic and prognostic utility. Detection methods include sequencing and immunohistochemistry for cytoplasmic NPM1 localization.

In research and clinical practice, NPM1 serves as both a functional marker of nucleolar biology and a molecular marker for AML classification and prognosis.