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Cytoplasmic mutated nucleophosmin (NPM) defines the molecular status of a significant fraction of myeloid sarcomas

Leukemia volume 21, pages 1566–1570 (2007)Cite this article

Detection of genetic lesions is critical for classification, prognostic stratification and monitoring of minimal residual disease of acute myeloid leukaemia (AML). Information on genetic lesions associated with myeloid sarcoma (MS), a tumor mass consisting of myeloblasts or immature myeloid cells at an extramedullary site,1 is still limited.2 This is mainly due to the fact that fresh cells are usually not available for cytogenetic and/or molecular studies. In fact, the diagnosis of MS is frequently unexpected and/or the size of the sample is small, such as a skin punch biopsy. Since MS is usually treated in the same way as AML, the frequent lack of available cytogenetics in MS represents a significant disadvantage, and the availability of techniques applicable to paraffin samples to detect specific genetic lesions would be of great help both for diagnostic and prognostic purposes.

Nucleophosmin (NPM) 1 mutations with consequent aberrant cytoplasmic expression of NPM3, 4 represent the most common genetic abnormality in AML, but no information is available on the role of NPM in MS. Since immunohistochemical detection of cytoplasmic NPM in AML predicts NPM1 mutations,5 we used anti-NPM antibodies4 to detect cytoplasmic/mutated NPM in 181 paraffin-embedded MS samples (characteristics of these cases are provided in the Supplementary Information). Immunohistochemical results were confirmed in a subset of cases by a PCR assay that we developed for application on formalin-fixed samples. We found 26 NPMc+ MS, whose biological and clinical features are reported here.

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Acknowledgements

Supported by the Associazione Italiana per la Ricerca sul Cancro (A.I.R.C.), BolognAIL, and Deutsche Krebshilfe (70-3173-Tr3). NB is a recipient of a fellowship from FIRC (Federazione Italiana per la Ricerca sul Cancro). We thank Dr Geraldine Boyd for editing the manuscript, Nicole Lange, Barbara Bigerna, Alessandra Pucciarini and Roberta Pacini for the excellent technical support, and Mrs Claudia Tibidò for secretarial assistance. Brunangelo Falini applied for a patent on the clinical use of NPM mutants.

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Authors and Affiliations

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

    B Falini, N Bolli, V Pettirossi, A Santucci & M F Martelli

  2. Campus Benjamin Franklin, Charitè-Universitatsmedizin, Berlin, Germany

    D Lenze, S Coupland, D Jaehne & H Stein

  3. Department of Pathology, Massachusetts General Hospital, Boston, USA

    R Hasserjian & C Soupir

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

    A Liso

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

    M P Martelli

  6. Istitute of Haematology and Clinical Oncology ‘L. and A. Seragnoli’ and Unit of Haematopathology, Policlinico S. Orsola, University of Bologna, Bologna, Italy

    F Bacci & S Pileri

Authors
  1. B Falini
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  2. D Lenze
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  3. R Hasserjian
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  4. S Coupland
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  5. D Jaehne
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  6. C Soupir
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  7. A Liso
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  8. M P Martelli
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  9. N Bolli
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  10. F Bacci
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  11. V Pettirossi
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  12. A Santucci
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  13. M F Martelli
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  14. S Pileri
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  15. H Stein
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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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Falini, B., Lenze, D., Hasserjian, R. et al. Cytoplasmic mutated nucleophosmin (NPM) defines the molecular status of a significant fraction of myeloid sarcomas. Leukemia 21, 1566–1570 (2007). https://doi.org/10.1038/sj.leu.2404699

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