Nucleophosmin (NPM1) (NPM1)

Nucleophosmin (NPM1) is a multifunctional nucleolar phosphoprotein that is essential for ribosome biogenesis, centrosome duplication, and genomic stability (UniProt P06748). While primarily localized in the nucleolus, NPM1 undergoes an unconventional translocation to the cell surface (csNPM) in various cancers, most notably in acute myeloid leukemia (AML) and certain solid tumors (Qi et al., 2018). This cell surface expression is highly tumor-specific, as normal cells typically restrict NPM1 to the nucleus, thereby providing a unique therapeutic window for targeted oncology treatments. Therapeutic strategies include the use of peptides like CIGB-300, which disrupts NPM1's chaperone functions and phosphorylation, as well as emerging immunotherapies like monoclonal antibodies and CAR-T cells that specifically recognize the surface-exposed protein. Targeting csNPM is particularly promising for treating AML patients, including those with the common NPM1 mutation, by inducing direct apoptosis or immune-mediated clearance of malignant cells. Its role as a surface marker also allows for its use as a diagnostic and prognostic biomarker in hematological malignancies.

Other names

B23Nucleolar phosphoprotein B23NutraminNO38NPM

CIGB-300 is a synthetic peptide that binds to the phospho-acceptor domain of NPM1, preventing its phosphorylation by protein kinase CK2 and inducing apoptosis (Perea et al., 2004). Other experimental agents like CAR-T cells and monoclonal antibodies target the cell surface-localized form of the protein (csNPM) to induce direct cell lysis or immune-mediated destruction (Qi et al., 2018).