A monoclonal antibody against mutated nucleophosmin 1 for the molecular diagnosis of acute myeloid leukemias

Alicja M. Gruszka, Serena Lavorgna, Maria Irno Consalvo, Tiziana Ottone, Chiara Martinelli, Mario Cinquanta, Giuseppe Ossolengo, Giancarlo Pruneri, Francesco Buccisano, Mariadomenica Divona, Michele Cedrone, Emanuele Ammatuna, Adriano Venditti, Ario De Marco, Francesco Lo-Coco, Pier Giuseppe Pelicci

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)2096-2102
Number of pages7
JournalBlood
Volume116
Issue number12
DOIs
Publication statusPublished - Sep 23 2010

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology
  • Medicine(all)

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  • Cite this

    Gruszka, A. M., Lavorgna, S., Consalvo, M. I., Ottone, T., Martinelli, C., Cinquanta, M., Ossolengo, G., Pruneri, G., Buccisano, F., Divona, M., Cedrone, M., Ammatuna, E., Venditti, A., De Marco, A., Lo-Coco, F., & Pelicci, P. G. (2010). A monoclonal antibody against mutated nucleophosmin 1 for the molecular diagnosis of acute myeloid leukemias. Blood, 116(12), 2096-2102. https://doi.org/10.1182/blood-2010-01-266908