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Nucleophosmin status may influence the therapeutic decision in de novo acute myeloid leukemia with normal karyotype

Leukemia volume 20, pages 1644–1646 (2006)Cite this article

Approximately 45% of patients with de novo acute myeloid leukemia (AML) have a normal karyotype (nk-AML).1 The complete remission (CR) rates for this group are around 80% with 5 years survival of 40–50%. The molecular heterogeneity of nk-AML has been recently described and may relate to prognostic stratification and new therapeutic approaches.2 Recently, Falini et al.3 reported a high incidence of heterozygous mutations in the gene coding for nucleophosmin (NPM), particularly in nk-AML. All mutations are located in exon 12 and are predicted to alter the protein structure at its C-terminal, causing delocalization of NPM from its normal nucleolar stores to the cytoplasm. Since this initial publication, six reports have investigated the prognostic value of NPM mutations in AML and consistently report better event-free survival (EFS) and overall survival (OS) in patients with mutated NPM (NPMm).4, 5 However, the good prognostic impact of NPM mutations may be hampered by its association to internal duplication of FLT3 (FLT3-ITD) mutations, which generally correlate with a worse outcome. Indeed, the favorable impact of NPM mutations on OS and EFS was detected only in the NPMm/FLT3-ITD− subgroup of patients. Here, we analyzed the clinical spectrum and prognostic value of NPM mutations in 110 patients with de novo nk-AML.

A major issue in nk-AML is to determine robust prognosis factors because of the marked heterogeneity in outcome. Despite this heterogeneity, most patients with an HLA-matched sibling are allocated to allo-SCT in first CR. However, a substantial proportion of patients may be cured with less toxic procedures such as ASCT or chemotherapy. Interestingly, Döhner et al.6 reported that allo-SCT did not improve the outcome of NPMm/FLT3-ITD− patients. In our series, NPMm/non-allografted patients did particularly well. Furthermore, we found that allo-SCT had a favorable impact only in the NPMwt patients. Indeed, the OS of the NPMwt patients who were not allografted was particularly poor. Although retrospective, these results suggest that the NPM status may define subgroups with risk-adapted therapy. If confirmed by large prospective studies, they should raise the question whether allo-SCT should be used only for the NPMwt patients.

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Acknowledgements

We thank all participating investigators from the GOELAMS protocol, Jessica Zuman-Rossi for valuable help and Veronique Della Valle for assistance in the initial steps of this work. This work was supported by ‘l'Association Laurette Fugain’ (www.laurettefugain.org).

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Author notes

  1. V Bardet and L D Costa: These authors contributed equally to this work

Authors and Affiliations

  1. Université Paris-Descartes, Faculté de Médecine et Service d'hématologie, Hôpital Cochin, AP-HP, Paris, France

    V Bardet, J Tamburini, F Dreyfus, C Lacombe & D Bouscary

  2. Institut Cochin, INSERM U567-CNRS-UMR 8104, Paris, France

    V Bardet, F Dreyfus, P Mayeux, C Lacombe & D Bouscary

  3. Laboratoire d'hématologie, Institut Gustave Roussy, Villejuif, France

    L D Costa

  4. Service d'informatique médicale et de biostatistique, Hôpital Cochin, AP-HP, Paris, France

    C Elie & O A Bernard

  5. E0210, INSERM IRNEM Hôpital Necker, Paris, France

    S Malinge & A Bennaceur-Griscelli

  6. Laboratoire d'hématologie, Hôpital Purpan, Toulouse, France

    C Demur

  7. Laboratoire d'hématologie, UPRES EA 3796 IFR 53, Reims, France

    P C Lefebvre

  8. Service d'hématologie, Hôpitaux de Brabois, Nancy, France

    F Witz

  9. Département d'hématologie et d'Oncologie, Hôpitaux Universitaires, Strasbourg, France

    B Lioure

  10. Service d'hématologie, Hôpital Caremeau, Nimes, France

    E Jourdan

  11. Service d'hématologie, Hôpital Dupuytren, Bordeaux, France

    A Pigneux

  12. Service des Maladies du Sang, CHU Angers, France

    N Ifrah

  13. Service d'hématologie, Hôpital Purpan, Toulouse, France

    M Attal & C Récher

Authors
  1. V Bardet
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  2. L D Costa
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  3. C Elie
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  4. S Malinge
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  11. A Pigneux
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  13. M Attal
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  14. F Dreyfus
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  15. P Mayeux
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  17. A Bennaceur-Griscelli
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  18. O A Bernard
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  19. D Bouscary
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  20. C Récher
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Consortia

for the GOELAMS: Groupe Ouest Est d'étude des Leucémies et des Autres Maladies du Sang

Corresponding author

Correspondence to C Récher.

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Bardet, V., Costa, L., Elie, C. et al. Nucleophosmin status may influence the therapeutic decision in de novo acute myeloid leukemia with normal karyotype. Leukemia 20, 1644–1646 (2006). https://doi.org/10.1038/sj.leu.2404294

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