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Annals of Hematology

, Volume 93, Issue 8, pp 1279–1286 | Cite as

Prognostic significance of FLT3 internal tandem duplication, nucleophosmin 1, and CEBPA gene mutations for acute myeloid leukemia patients with normal karyotype and younger than 60 years: a systematic review and meta-analysis

  • M. Port
  • M. Böttcher
  • F. Thol
  • A. Ganser
  • R. Schlenk
  • J. Wasem
  • A. Neumann
  • L. Pouryamout
Review Article

Abstract

Diagnosis and classification of acute myeloid leukemia (AML) are based on morphology and genetics. An increasing number of gene mutations have been found, and some are used for risk classification in AML patients with normal karyotype (cytogenetically normal (CN)-AML). In this systematic review and meta-analysis, we examined three frequent mutations in CN-AML: mutations of fms-related tyrosine kinase 3 (FLT3-ITD), mutated nucleophosmin (NPM1), and mutations of the CCAAT enhancer-binding protein alpha (CEBPA) gene. A systematic literature search of publications listed in the electronic databases (Embase, Pubmed, Healthstar, BIOSIS, ISI Web of Knowledge and Cochrane) from 2000 up to March 2012 was performed (Fig. 1). Nineteen studies were included and qualitatively analyzed. Two to four studies entered the quantitative meta-analysis incorporating 1,378 to 1,942 patients with CN-AML. Meta-analysis for overall survival (OS) and relapse-free survival (RFS) showed FLT3-ITD to predict an unfavorable prognosis, with hazard ratios (HR) of 1.86 and 1.75, respectively. In contrast, meta-analysis of the impact of NPM1 and CEBPA mutations on OS yielded an HR of 0.56 for each mutation, while analysis of impact on RFS produced HRs of 0.37 and 0.42, respectively. This systematic review and meta-analysis aimed to evaluate the prognostic value of mutations in the NPM1, CEBPA, and FLT3 genes. FLT3-ITD was associated with worse prognosis, whereas mutations in NPM1 and CEBPA genes were associated with a favorable prognosis.

Keywords

Acute myeloid leukemia Normal karyotype Mutations of fms-related tyrosine kinase 3 Mutated nucleophosmin Mutations of the CEBPA gene Meta-analysis 

Notes

Acknowledgment

This work was supported by the Bundesministerium für Bildung und Forschung/Germany.

We are very thankful to Michael Morgan carefully reading the manuscript.

Conflict of interest

All authors have no conflict of interest to declare.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • M. Port
    • 1
  • M. Böttcher
    • 1
  • F. Thol
    • 1
  • A. Ganser
    • 1
  • R. Schlenk
    • 2
  • J. Wasem
    • 3
  • A. Neumann
    • 3
  • L. Pouryamout
    • 3
  1. 1.Department of Hematology, Hemostasis, Oncology, and Stem Cell TransplantationHannover Medical School (MHH)HannoverGermany
  2. 2.Institute for Health Care Management and ResearchUniversity of Duisburg-EssenEssenGermany
  3. 3.Department of Internal Medicine IIIUniversity of UlmUlmGermany

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