Терапевтический архив (Dec 2010)

FLT3 and NPM1 gene mutations in patients with acute myeloid leukemias and the impact of FLT3-ITD mutations on the survival of patients with a normal karyotype

  • Irina Stepanovna Martynkevich,
  • Sergey Vasil'evich Gritsaev,
  • Mikhail Viktorovich Moskalenko,
  • Marina Petrovna Ivanova,
  • Vasilisa Yur'evna Aksenova,
  • Sof'ya Aleksandrovna Tiranova,
  • Kudrat Mugutdinovich Abdulkadyrov,
  • I S Martynkevich,
  • S V Gritsayev,
  • M V Moskalenko,
  • M P Ivanova,
  • V Yu Aksenova,
  • S A Tiranova,
  • K M Abdulkadyrov

Journal volume & issue
Vol. 82, no. 12
pp. 33 – 39

Abstract

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Aim. To estimate the extent of FLT3 and NPM1 gene mutations and the impact of mutations of FLT3-ITD on the survival of patients with acute myeloid leukemias (AML). Materials and methods. The nucleus-containing cells of bone marrow and blood were studied in 43 patients with AML. Polymerase chain reaction analysis of total genomic DNA was applied. Results. Mutations of FLT3-ITD, FLT3-TDK, and the NPM1 gene were found in 16 (37.2%) patients. A total of 19 mutations were revealed. There were 8 mutations of FLT3-ITD, 5 of FLT3-TKD, and 6 in the NPM1 gene. Single damages to genes were detected in 13 patients: FLT3-ITD in 6 (13.9%), FLT3-TKD in 4 (9.3%), and NPM1 in 3 (7%). Three (7%) patients exhibited 2 mutations simultaneously: in the NPM1 and FLT3-ITD in 2 (4.7%) and in the NPM1 gene and FLT3-TKD in 1 (2.3%). In AML patients with a normal karyotype and the FLT3-ITD-/NPM1- and FLT3-ITD+/ NPM1- genotypes, median overall survival was 17.3 versus 8 months (p = 0.069); and event-free survival (EFS) was 11 versus 5 months (p = 0.026). Univariate analysis established the negative impact of FLT3-ITD mutation on EFS. Conclusion. The findings allow AML patients with a normal karyotype and the FLT3-ITD-/NPM1- genotypes to be identified as a poor prognosis group.

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