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Age-dependent frequencies of NPM1 mutations and FLT3-ITD in patients with normal karyotype AML (NK-AML)

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Abstract

Prognosis of AML in elderly patients is poor due to adverse patient characteristics and comorbidities. In addition, disease-associated parameters reveal differences between older and younger patients with AML. Survival in normal karyotype AML (NK-AML) is influenced by different clinical and molecular markers. The aim of this work was to investigate the frequencies of molecular markers in patients with NK-AML with a focus on NPM1 mutations and FLT3-ITD in different age groups. In the present study, we analyzed the frequencies of mutations of NPM1 and FLT3-ITD in a cohort of 1,321 adult patients and 148 children with AML treated within the AMLCG99, the AML98, and AML04 trials and their distribution in different age groups. Additionally, the frequencies of mutations in CEBPA genes, FLT3-TKD, and MLL-PTD were analyzed in the cohort with NK-AML (n = 729). Our data show that the presence of mutations of NPM1 (from 60% to 40%) and FLT3-ITD (from 50% to 20%) significantly decreased with age in adult AML. Consequently, the proportion of NPM1−/FLT3-ITD− patients increased with age. The decreasing frequency of NPM1 mutations in elderly patients was paralleled by a reduced complete remission (CR) rate in the elderly of 55% compared to 80% in the younger patients. By contrast, the frequencies of other gene mutations, like FLT3-TKD and MLL-PTD, and mutations in CEBPA were not age-dependent. The decreasing frequency of the favorable NPM1 mutations with increasing age may partially explain the worse outcome in the elderly patients. Furthermore, the increasing amount of elderly patients without NPM1 mutations or FLT3-ITD suggests that other molecular and clinical risk factors may influence prognosis in this age group.

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Acknowledgments

The authors would like to thank Gudrun Mellert and Evelyn Zellmeier (Laboratory for Leukemia Diagnostics, University Hospital Munich) for their excellent technical support.

Conflict of interest

The author indicates no potential conflict of interest.

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Authors and Affiliations

  1. Laboratory for Leukemia Diagnostics Department of Medicine III, University Hospital Munich, Campus Grosshadern Marchioninistr. 15, 81377, Munich, Germany

    Friederike Schneider, Eva Hoster, Stephanie Schneider, Annika Dufour, Tobias Benthaus, Purvi M. Kakadia, Stefan K. Bohlander, Jan Braess, Wolfgang Hiddemann & Karsten Spiekermann

  2. Clinical Cooperative Group Acute Leukemias, Helmholtz Center Munich, Munich, Germany

    Stefan K. Bohlander, Wolfgang Hiddemann & Karsten Spiekermann

  3. Institute of Biostatistics and Clinical Research, University of Muenster, Muenster, Germany

    Achim Heinecke & Maria C. Sauerland

  4. Department of Medicine, Hematology and Oncology, University of Muenster, Muenster, Germany

    Wolfgang E. Berdel & Thomas Buechner

  5. German Society of Hematology and Oncology, Berlin, Germany

    Bernhard J. Woermann

  6. Department of Internal Medicine III, University of Ulm, Ulm, Germany

    Michaela Feuring-Buske & Christian Buske

  7. Comprehensive Cancer Center Ulm, Institute of Experimental Tumor Research, Ulm, Germany

    Christian Buske

  8. Department of Pediatric Hematology and Oncology, University of Muenster, Muenster, Germany

    Ursula Creutzig

  9. Department of Medicine I, University Hospital Dresden, Dresden, Germany

    Christian Thiede

  10. Department of Pediatric Oncology and Hematology, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands

    Michel C. Zwaan & Marry M. van den Heuvel-Eibrink

  11. AML-BFM Study Group, Department of Pediatric Oncology/Hematology, Medical High School, Hannover, Germany

    Dirk Reinhardt

  12. Department of Medicine III, University Hospital Grosshadern, Marchioninistr. 15, 81377, Munich, Germany

    Friederike Schneider

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  1. Friederike Schneider
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  2. Eva Hoster
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  3. Stephanie Schneider
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Correspondence to Friederike Schneider.

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Overview of patient cohorts (DOC 41 kb)

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Schneider, F., Hoster, E., Schneider, S. et al. Age-dependent frequencies of NPM1 mutations and FLT3-ITD in patients with normal karyotype AML (NK-AML). Ann Hematol 91, 9–18 (2012). https://doi.org/10.1007/s00277-011-1280-6

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