NPM1 (C Mutant Specific) Antibody #17944

Nucleophosmin (NPM1; also known as NPM, B23, numatrin, or NO38) is an abundant phosphoprotein primarily found in nucleoli. It has been implicated in several distinct cellular functions, including assembly and transport of ribosomes, cytoplasmic/nuclear trafficking, regulation of DNA polymerase α activity, centrosome duplication, and molecular chaperoning activities (1,2). The NPM1 gene is also known for its fusion with the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase. The NPM1 portion contributes to transformation by providing a dimerization domain, which results in activation of the fused kinase (3,4). NPM1 is also the most frequently mutated gene in acute myeloid leukemia (AML) and accounts for nearly 30% of all cases (5). These AML subtypes, classified as NPM1-mutated AML, are characterized by mutations in NPM1’s C-terminus that disrupt its nucleolar localization sequence and cause mislocalization from the nucleolus to the cytoplasm (6). This cytoplasmic form of NPM1, commonly referred to as NPM1c, is exclusive to myeloid malignancies and is not found in other forms of cancer (7). These mutations are always heterozygous, and NPM1c functions in a dominant negative fashion by dimerizing with wild-type NPM1 and recruiting it to the cytoplasm (6,8). Interestingly, NPM1 mutations alone are not sufficient to drive leukemogenesis, and further research is required to fully elucidate the impact of these mutations on disease progression (9).