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Nucleophosmin leukaemic mutants contain C-terminus peptides that bind HLA class I molecules

Leukemia volume 22, pages 424–426 (2008)Cite this article

Acute myeloid leukaemia (AML) is a clinically and molecularly heterogeneous disease and its treatment remains challenging since only 30% of patients achieve long-term disease-free survival.1 Evidence that immunological control contributes to killing of residual leukaemia cells has emerged from allogeneic haematopoietic stem cell transplantation,2 and immunotherapy holds promise as a possible new treatment, in combination with chemotherapy, to eradicate minimal residual disease.

We recently identified mutations of the nucleophosmin (NPM1) gene as the most common genetic lesion in adult AML, occurring in about one-third of patients.3 AML carrying NPM1 mutations represents an entity with distinctive biological and clinical features4 and the unique C-terminal sequences of NPM leukaemic mutants have the potential to serve as target for immunotherapeutic intervention. We addressed this issue using the BLAST web tool (http://www.ncbi.nlm.nih.gov/blast) to search for short sequences matching the NPM mutants A–F. None of the human sequences present in databanks matched that of the 11 C-terminal residues of the NPM mutants, suggesting that this sequence may serve as leukaemia-specific antigen.

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Acknowledgements

This work was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC), University of Foggia Research Grants 2004–2005 and by grants from the Fondation contre le Cancer, Brussels, Belgium. Brunangelo Falini applied for a patent on the clinical use of NPM mutants. The other authors report no potential conflicts of interest.

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Authors and Affiliations

  1. Haematology Section, University of Foggia, Foggia, Italy

    A Liso

  2. Christian de Duve Institute of Cellular Pathology, Université catholique de Louvain, Brussels, Belgium

    D Colau, R Benmaamar & P Coulie

  3. Epivax Inc., Providence, RI, USA

    A De Groot & W Martin

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

    R Benedetti & B Falini

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

    G Specchia & M P Martelli

Authors
  1. A Liso
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  2. D Colau
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  3. R Benmaamar
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  4. A De Groot
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  5. W Martin
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  6. R Benedetti
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  7. G Specchia
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  8. M P Martelli
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  9. P Coulie
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  10. B Falini
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Corresponding authors

Correspondence to A Liso or B Falini.

Additional information

Authors' contributions: AL designed the study, performed experiments, wrote manuscript draft; DC, RB and PC performed experiments and revised manuscript draft; GS and MPM treated patients, provided sample material, revised manuscript draft; RB performed experiments and revised manuscript draft; ADG and WM performed in silico experiments and revised manuscript; BF supervised the study and revised the manuscript.

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Liso, A., Colau, D., Benmaamar, R. et al. Nucleophosmin leukaemic mutants contain C-terminus peptides that bind HLA class I molecules. Leukemia 22, 424–426 (2008). https://doi.org/10.1038/sj.leu.2404887

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