Clinical relevance of FLT3 gene abnormalities in Brazilian patients with infant leukemia.
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.
Emerenciano
Mariana
M
Pediatric Hematology-Oncology Program, Research Center, Instituto Nacional de Cancer, Brazil.
Menezes
Juliane
J
Vasquez
Marina Lipkin
ML
Zalcberg
Ilana
I
Thuler
Luiz Claudio Santos
LC
Pombo-de-Oliveira
Maria S
MS
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*
D051788:Myeloid-Lymphoid Leukemia Protein; D051941:fms-Like Tyrosine Kinase 3