Clinical relevance of FLT3 gene abnormalities in Brazilian patients with infant leukemia

Leuk Lymphoma. 2008 Dec;49(12):2291-7. doi: 10.1080/10428190802491698.

Abstract

Infant leukemia (IL) is characterised by the presence of MLL rearrangements and a poor outcome. FLT3 gene is consistently highly expressed in MLL+ patients. To correlate the clinical aspects of IL with FLT3 sequence alterations, we have analysed 159 children included in the Brazilian Collaborative Study Group of Infant Acute Leukemia. FLT3-D835 mutations and FLT3-ITD were detected by PCR-RFLP assay and standard PCR amplification, respectively. Mean age at diagnosis was 11.3 months. Overall, 7.5% (ITDs n=6 and D835 n=6) of patients contained FLT3 mutations. FLT3 mutated cases exhibited significantly higher white blood cells (WBC) than wild-type patients (p=0.013). Median overall survival time was 9.2 months (SE 3.3, 95% CI 2.8-15.6). Variables with significant poorer outcomes were age<6 months (p=0.0043), MLL+ (p=0.0292), AML subtype (p=0.0008), high WBC (p=0.0179) and FLT3-D835 mutation (p=0.042). The concomitant presence of FLT3 and MLL abnormalities displayed the worst survival (p=0.0032). Cox regression analysis, with survival as endpoint, showed that leukemia subtype and WBC were independent prognostic factors. Although FLT3 mutations were not a frequent genetic abnormality in this cohort, they might be prognostically important in IL, but this will need to be confirmed in the analyses of larger patient cohorts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brazil
  • DNA Mutational Analysis / methods
  • Humans
  • Infant
  • Infant, Newborn
  • Inverted Repeat Sequences
  • Leukemia / epidemiology
  • Leukemia / genetics*
  • Leukocyte Count
  • Mutation, Missense
  • Myeloid-Lymphoid Leukemia Protein / genetics
  • Prognosis
  • Retrospective Studies
  • Survival Rate
  • fms-Like Tyrosine Kinase 3 / genetics*

Substances

  • Myeloid-Lymphoid Leukemia Protein
  • fms-Like Tyrosine Kinase 3