A monoclonal antibody against mutated nucleophosmin 1 for the molecular diagnosis of acute myeloid leukemias.
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.
Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
Alicja M
AM
Gruszka
Serena
S
Lavorgna
Maria Irno
MI
Consalvo
Tiziana
T
Ottone
Chiara
C
Martinelli
Mario
M
Cinquanta
Giuseppe
G
Ossolengo
Giancarlo
G
Pruneri
Francesco
F
Buccisano
Mariadomenica
M
Divona
Michele
M
Cedrone
Emanuele
E
Ammatuna
Adriano
A
Venditti
Ario
A
de Marco
Francesco
F
Lo-Coco
Pier Giuseppe
PG
Pelicci
D000911:Antibodies, Monoclonal; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis*; D025202:Molecular Diagnostic Techniques; D050505:Mutant Proteins / Q000276:immunology; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000276:immunology; D000090243:Nucleophosmin; D010446:Peptide Fragments / Q000276:immunology
D000911:Antibodies, Monoclonal; D050505:Mutant Proteins; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D010446:Peptide Fragments; D000090243:Nucleophosmin