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Absence of nucleophosmin leukaemic mutants in B and T cells from AML with NPM1 mutations: implications for the cell of origin of NPMc+ AML

Leukemia volume 22, pages 195–198 (2008)Cite this article

Studies of cell lineage involvement and of cell origin in acute myeloid leukaemia with normal karyotype (AML-NK) have traditionally been hampered by the lack of clonality markers. Recently, we identified NPM1 mutations as the most common genetic alteration occurring in AML-NK (50–60% of cases).1, 2 NPM1 mutations represent an ideal genetic lesion for tracking cell lineage involvement in AML, as they are usually expressed in all leukaemic cells1 and are very stable.2 More importantly, NPM1 mutations generate NPM mutated proteins which are aberrantly expressed in the cytoplasm of leukaemic cells.3 Thus, NPM cytoplasmic positivity (NPMc+) represents a unique tool for studying by immunohistochemistry cell lineage involvement4 in fixed paraffin-embedded bone marrow samples from NPMc+ AML patients.

Combining immunohistochemistry with analysis of NPM1 mutations on laser-microdissected haemopoietic cells, we found involvement of two or more myeloid lineages in a large proportion of NPMc+ AML.4 However, whether lymphoid lineages are also involved in NPMc+ AML still remains an open question. Immunohistochemical analysis of reactive lymphoid nodules in bone marrow biopsies from three NPMc+ AML patients did not reveal aberrant cytoplasmic dislocation of NPM,4 suggesting that lymphoid cells are not targeted by NPM1 mutations. However, reactive lymphoid nodules may not be representative of the B- and T-cell populations resident in the bone marrow or circulating in the peripheral blood of NPMc+ AML patients. Moreover, the data were obtained only in three patients, and therefore, it cannot be excluded that lymphoid cells may be involved in a proportion of NPMc+ AML cases. For example, it is known that certain myeloid-associated mutations (such as JAK2V617) can be detected in lymphoid cells of only a percentage of idiopathic myelofibrosis and polycythemia vera5 cases. Thus, the possibility that lymphoid cells derive from the neoplastic clone in some cases of NPMc+ AML is not yet fully clarified.

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Acknowledgements

This work was supported by Associazione Italiana per la Ricerca sul Cancro (AIRC) and Fondazione Monte dei Paschi di Siena. NB is a recipient of a fellowship from Federazione Italiana per la Ricerca sul Cancro. We thank Debora Cecchini for performing FACS analysis of AML samples, 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 NPM mutants.

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Authors and Affiliations

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

    M P Martelli & G Specchia

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

    N Manes, V Pettirossi, R Pacini, R Mannucci, T Zei, N Bolli, I Nicoletti, M F Martelli & B Falini

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

    A Liso

  4. Istitute of Haematology, University of Catania, Catania, Italy

    F di Raimondo

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  1. M P Martelli
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Correspondence to B Falini.

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

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Martelli, M., Manes, N., Pettirossi, V. et al. Absence of nucleophosmin leukaemic mutants in B and T cells from AML with NPM1 mutations: implications for the cell of origin of NPMc+ AML. Leukemia 22, 195–198 (2008). https://doi.org/10.1038/sj.leu.2404857

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