Mutations in the nucleophosmin 1 (NPM1) gene are the most frequent genetic aberrations of acute myeloid leukemia (AML) and define a clinically distinct subset of AML. A monoclonal antibody (T26) was raised against a 19-amino acid polypeptide containing the unique C-terminus of the type A NPM1 mutant protein. T26 recognized 10 of the 21 known NPM1 mutants, including the A, B, and D types, which cover approximately 95% of all cases, and did not cross-react with wild-type NPM1 or unrelated cellular proteins. It performed efficiently with different detection technologies, including immunofluorescence, immunohistochemistry, and flow cytometry. Within a series of consecutive de novo AML patients, 44 of 110 (40%) and 15 of 39 (38%) cases scored positive using the T26 antibody in immunofluorescence and flow cytometry assays, respectively. T26-positive cases were found to be all carrying mutations of NPM1 exclusively, as determined by molecular analysis. T26 is the first antibody that specifically recognizes a leukemia-associated mutant protein. Immunofluorescence or flow cytometry using T26 may thus become a new tool for a rapid, simple, and cost-effective molecular diagnosis of AMLs.
ASJC Scopus subject areas
- Cell Biology