title: 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.
authors.affiliation: Pediatric Hematology-Oncology Program, Research Center, Instituto Nacional de Cancer, Brazil.
authors.forename: Mariana
authors.initials: M
authors.lastname: Emerenciano
authors.forename: Juliane
authors.initials: J
authors.lastname: Menezes
authors.forename: Marina Lipkin
authors.initials: ML
authors.lastname: Vasquez
authors.forename: Ilana
authors.initials: I
authors.lastname: Zalcberg
authors.forename: Luiz Claudio Santos
authors.initials: LC
authors.lastname: Thuler
authors.forename: Maria S
authors.initials: MS
authors.lastname: Pombo-de-Oliveira
mesh_terms: D001938:Brazil; D004252:DNA Mutational Analysis / Q000379:methods; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D055029:Inverted Repeat Sequences; D007938:Leukemia / Q000453:epidemiology / Q000235:genetics*; D007958:Leukocyte Count; D020125:Mutation, Missense; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: D051788:Myeloid-Lymphoid Leukemia Protein; D051941:fms-Like Tyrosine Kinase 3