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Minimal Residual Disease

Quantitative assessment of minimal residual disease in acute myeloid leukemia carrying nucleophosmin (NPM1) gene mutations

Leukemia volume 20, pages 1103–1108 (2006)Cite this article

Abstract

Mutations in exon 12 of the nucleophosmin (NPM1) gene occur in about 60% of adult AML with normal karyotype. By exploiting a specific feature of NPM1 mutants, that is insertion at residue 956 or deletion/insertion at residue 960, we developed highly sensitive, real-time quantitative (RQ) polymerase chain reaction (PCR) assays, either in DNA or RNA, that are specific for various NPM1 mutations. In all 13 AML patients carrying NPM1 mutations at diagnosis, cDNA RQ-PCR showed >30 000 copies of NPM1-mutated transcript. A small or no decrease in copies was observed in three patients showing partial or no response to induction therapy. The number of NPM1-mutated copies was markedly reduced in 10 patients achieving complete hematological remission (five cases: <100 copies; five cases: 580–5046 copies). In four patients studied at different time intervals, the number of NPM1 copies closely correlated with clinical status and predicted impending hematological relapse in two. Thus, reliable, sensitive RQ-PCR assays for NPM1 mutations can now monitor and quantify MRD in AML patients with normal karyotype and NPM1 gene mutations.

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Acknowledgements

This work was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC), Ministero Istruzione Università e Ricerca, Associazione Umbra Studio e Terapia Leucemie e Linfomi (AULL), Fondazione Cassa di Risparmio di Perugia Fondazione Tettamanti, Fondazione Cariplo. Federica Alberti's work was supported by the Progetto Lagrange-Fondazione CRT e Fondazione ISI Turin. The authors would like to thank Marco Cappelletti (Applera Italia) and Amplimedical SpA (Buttigliera Alta, Turin, Italy) for collaboration and technical support.

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Author notes

  1. P Gorello and G Cazzaniga: These two authors contributed equally to this study.

Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, Institute of Hematology, University of Perugia, Perugia, Italy

    P Gorello, G Roti, R Rosati, M F Martelli, C Mecucci & B Falini

  2. M Tettamanti Research Centre, University of Milano-Bicocca, St Gerard's Hospital, Monza, Italy

    G Cazzaniga, M G Dell'Oro & A Biondi

  3. Division of Hematology and Internal Medicine, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy

    F Alberti, E Gottardi & G Saglio

  4. Department of Hematology, University of Bari, Bari, Italy

    G Specchia

  5. Department of Cellular Biotechnologies and Hematology ‘La Sapienza’ University, Rome, Italy

    D Diverio

  6. Department of Biopathology, ‘Tor Vergata’ University, Rome, Italy

    F Lo Coco

Authors
  1. P Gorello
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  2. G Cazzaniga
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  3. F Alberti
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  4. M G Dell'Oro
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  5. E Gottardi
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  6. G Specchia
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  7. G Roti
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  8. R Rosati
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  9. M F Martelli
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  10. D Diverio
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  11. F Lo Coco
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  12. A Biondi
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  13. G Saglio
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  14. C Mecucci
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  15. B Falini
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Corresponding author

Correspondence to C Mecucci.

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Gorello, P., Cazzaniga, G., Alberti, F. et al. Quantitative assessment of minimal residual disease in acute myeloid leukemia carrying nucleophosmin (NPM1) gene mutations. Leukemia 20, 1103–1108 (2006). https://doi.org/10.1038/sj.leu.2404149

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  • DOI: https://doi.org/10.1038/sj.leu.2404149

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