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NPM1-mutated acute myeloid leukaemia occurring in JAK2-V617F+ primary myelofibrosis: de-novo origin?

Leukemia volume 22, pages 1459–1463 (2008)Cite this article

Acute myeloid leukaemia (AML) carrying mutated NPM1 and cytoplasmic nucleophosmin (NPM) protein (NPMc+AML)1 accounts for about one-third of adult AML (50–60% of AML with normal karyotype), and shows distinctive biological and clinical features.2 NPM1 mutations are mutually exclusive of recurrent genetic abnormalities and characteristically associate with de novo AML.1, 2 We report for the first time a patient who developed AML with NPM1 mutation 6 years after a JAK2-V617F+ primary myelofibrosis (PMF).

In May 2006, the patient received chemotherapy according to the MICE schedule (mitoxantrone, ARA-C, etoposide). One month later, a bone marrow aspirate and biopsy showed a complete haematological remission. Two consolidation cycles with the mini-ICE schedule (idarubicin, ARA-C, etoposide) were completed in August 2006 and, at the last control (November 2007), the patient remains in complete haematological remission and the number of platelets is presently within the normal range. Notably, a quantitative PCR assay (sensitivity 1 × 106) carried out in March 2007 showed no residual copies of NPM mutant A transcripts, a finding indicative of a molecular remission (Supplementary Figure 1). At that time, a JAK2-V617F mutation was detected in about 40% of marrow haemopoietic cells.

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Acknowledgements

This study was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) to BF and by grants 310000-108006/1 from the Swiss National Science Foundation and the Swiss Cancer League (OCS-01742-08-2005) to RCS. We are grateful to Dr GA Boyd for editorial assistance. BF has applied for a patent on the clinical use of NPM mutants.

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Author notes

  1. L Pasqualucci and S Li: These authors contributed equally to the work

Authors and Affiliations

  1. Section of Haematology and Immunology, University of Perugia, IBit Foundation, Perugia, Italy

    L Pasqualucci, M Di Ianni, M P Martelli & B Falini

  2. Institute for Cancer Genetics and the Department of Pathology, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA

    L Pasqualucci

  3. Department of Research, Experimental Hematology, University Hospital Basel, Basel, Switzerland

    S Li & R C Skoda

  4. Department of Cellular Biotechnologies and Haematology, University ‘La Sapienza’, Rome, Italy

    G Meloni, E Pescarmona & R Foa

  5. MLL Munich Leukemia Laboratory, Max-Lebsche-Platz 31, Munich, Germany

    S Schnittger & T Haferlach

  6. Institute of Pathology, University of Wurzburg, Wurzburg, Germany

    S Gattenlohner

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

    A Liso

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  1. L Pasqualucci
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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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Pasqualucci, L., Li, S., Meloni, G. et al. NPM1-mutated acute myeloid leukaemia occurring in JAK2-V617F+ primary myelofibrosis: de-novo origin?. Leukemia 22, 1459–1463 (2008). https://doi.org/10.1038/sj.leu.2405093

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