Internal tandem duplication of the FLT3 gene and clinical evaluation in childhood acute myeloid leukemia. The Children's Cancer and Leukemia Study Group, Japan

Leukemia. 1999 Jan;13(1):38-43. doi: 10.1038/sj.leu.2401241.


We analyzed tandem duplication in the juxtamembrane (JM) domain of the FLT3 (FMS-like tyrosine kinase 3/FLK2, CD135) gene in 94 children with acute myeloid leukemia (AML) and evaluated its correlation with clinical features. Longer polymerase chain reaction (PCR) products were observed in five patients; 1/3 of M0, 119 of M1, 1/39 of M2, 1/9 of M3 and 1/12 of M5. The sequence analyses of abnormal PCR products showed that all the abnormal products were derived from tandem duplications involving the JM domain and that all the lengthened sequences were in-frame as we previously reported. Statistical analyses revealed a significantly lower incidence of the tandem duplication in childhood AML patients than in adult patients (P < 0.05), and significantly shorter disease-free survival in patients with mutant FLT3 than in patients with wild-type FLT3 (P < 0.05). Our results suggest that the tandem duplication in the JM domain of the FLT3 gene is not a frequent phenomenon but might be a factor of poor prognosis in childhood patients with AML.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • Acute Disease
  • Adult
  • Amino Acid Sequence
  • Bone Marrow / pathology
  • Child
  • Exons
  • Female
  • Gene Duplication*
  • Humans
  • Introns
  • Leukemia, Myeloid / blood
  • Leukemia, Myeloid / genetics*
  • Leukemia, Myeloid / mortality
  • Leukemia, Myeloid / pathology
  • Male
  • Molecular Sequence Data
  • Phosphorylation
  • Polymerase Chain Reaction
  • Prognosis
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogenes*
  • Receptor Protein-Tyrosine Kinases / chemistry
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptors, Cell Surface / genetics
  • Repetitive Sequences, Amino Acid
  • Survival Analysis
  • fms-Like Tyrosine Kinase 3


  • Proto-Oncogene Proteins
  • Receptors, Cell Surface
  • FLT3 protein, human
  • Receptor Protein-Tyrosine Kinases
  • fms-Like Tyrosine Kinase 3