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A western blot assay for detecting mutant nucleophosmin (NPM1) proteins in acute myeloid leukaemia

Leukemia volume 22, pages 2285–2288 (2008)Cite this article

Acute myeloid leukaemia (AML) carrying a mutated NPM1 gene and aberrant dislocation of nucleophosmin (NPM1) into the cytoplasm1 accounts for about one-third of adult AML and shows distinctive biological and clinical features.2, 3, 4 AML with normal karyotype and mutated NPM1, in the absence of FLT3-ITD, exhibits a favourable prognosis.2 Moreover, NPM1 mutations may serve as a marker for monitoring minimal residual disease.2 Thus, the search for NPM1 mutations has now become part of the initial diagnostic work-up in patients with AML.

Approximately 40 different molecular variants of NPM1 mutations,2 the most frequent genetic alteration in AML, have been identified so far (Supplementary Table 1). Mutation A is the most common type (75–80% cases)1 and mutations B and D account for about 10 and 5% of NPM1-mutated AML, respectively; other mutations are very rare.2 Although several sensitive molecular techniques detect NPM1 mutations in DNA or RNA,2 a demand has arisen for simpler, less expensive diagnostic assays, which are suitable for centres that are not equipped for molecular screening. Availability of such tests would contribute to expand the use of a genetic-based WHO classification of AML.

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Acknowledgements

This work was supported by Associazione Italiana per la Ricerca sul Cancro (A.I.R.C.) and Fondazione Monte dei Paschi di Siena. We thank Roberta Pacini and Manola Carini for performing immunohistochemical staining. We also thank Dr Geraldine Boyd, for editing the manuscript, and Mrs Claudia Tibidò, for secretarial assistance. Brunangelo Falini applied for a patent on the clinical use of NPM1 mutants.

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Author notes

  1. N Manes and A Liso: These authors contributed equally to this work.

Authors and Affiliations

  1. Section of Haematology and Clinical Immunology, University of Perugia, IBiT Foundation, Fondazione IRCCS Biotecnologie nel trapianto, Perugia, Italy

    M P Martelli, N Manes, V Pettirossi, B Verducci Galletti, B Bigerna, A Pucciarini, M F De Marco, M T Pallotta, N Bolli, M F Martelli & B Falini

  2. Institute of Haematology, University of Foggia, Foggia, Italy

    A Liso

  3. Haematology Branch, Ospedale di Pescara, Pescara, Italy

    M Sborgia

  4. Haematology Branch, Ospedale Ferrarotto S. Bambino, Catania, Italy

    F di Raimondo

  5. Haematology Branch, Ospedale V. Cervello, Palermo, Italy

    F Fabbiano

  6. Haematology, ‘La Sapienza’ University, Rome, Italy

    G Meloni

  7. Institute of Haematology, University of Bari, Bari, Italy

    G Specchia

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Corresponding author

Correspondence to B Falini.

Additional information

Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Martelli, M., Manes, N., Liso, A. et al. A western blot assay for detecting mutant nucleophosmin (NPM1) proteins in acute myeloid leukaemia. Leukemia 22, 2285–2288 (2008). https://doi.org/10.1038/leu.2008.149

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