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

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.

Keywords:

• Acute lymphoblastic leukemia
• acute myeloid leukemia
• FLT3
• hyperdiploid
• infant acute leukemia
• MLL