Medical Oncology

, Volume 27, Issue 3, pp 640–645

Incidence of FLT3 and nucleophosmin gene mutations in childhood acute myeloid leukemia: Serbian experience and the review of the literature

  • Nada Krstovski
  • Natasa Tosic
  • Dragana Janic
  • Lidija Dokmanovic
  • Milos Kuzmanovic
  • Vesna Spasovski
  • Sonja Pavlovic
Original Paper

DOI: 10.1007/s12032-009-9261-5

Cite this article as:
Krstovski, N., Tosic, N., Janic, D. et al. Med Oncol (2010) 27: 640. doi:10.1007/s12032-009-9261-5

Abstract

Mutations in the fms-like tyrosine kinase 3 (FLT3) gene (internal tandem duplication (ITD) and point mutation in the tyrosine kinase domain, FLT3/D835) as well as the nucleophosmin (NPM1) gene are the most common abnormalities in adult acute myeloid leukemia (AML). Their significance in pediatric AML is still unclear. In this study we evaluated the frequency of FLT3 and NPM1 mutations in childhood AML. We also examined clinical features and outcome of these patients. FLT3 and NPM1 mutations were analysed in 42 and 37 childhood AML patients, respectively, using polymerase chain reaction (PCR) and direct sequencing. FLT3 mutations were detected in 4/42 patients (9.5%). The frequencies of FLT3/ITD and FLT3/D835 were the same, 2/42 (4.7%). NMP1 mutations were found in 1/37 patients (2.7%). FLT3 gene mutations were correlated with induction failure. Here we report the results of the study of FLT3 and NPM1 gene mutations in childhood AML patients in Serbia. Low frequencies of these molecular markers point out that these abnormalities are rare in this cohort of patients. Comparative study of data on NPM1 mutations in childhood AML revealed that various NPM1 gene mutation types are associated with childhood AML. Our findings as well as previously reported data, contributes to a hypothesis of different biology and etiology of adult and childhood AML. More extensive studies of NPM1 and FLT3 mutations in childhood AML are needed to determine their biological and clinical importance.

Keywords

FLT3 mutationsNMP1 mutationsAcute myeloid leukemiaChildren

Copyright information

© Humana Press Inc. 2009

Authors and Affiliations

  • Nada Krstovski
    • 1
  • Natasa Tosic
    • 2
  • Dragana Janic
    • 1
  • Lidija Dokmanovic
    • 1
  • Milos Kuzmanovic
    • 3
  • Vesna Spasovski
    • 2
  • Sonja Pavlovic
    • 2
  1. 1.Department of Hematology/OncologyUniversity Children Hospital, Medical Faculty University of BelgradeBelgradeSerbia
  2. 2.Laboratory for Molecular HematologyInstitute of Molecular Genetics and Genetic EngineeringBelgradeSerbia
  3. 3.Department of HematologyMother and Child Healthcare Institute “Dr Vukan Cupic”BelgradeSerbia