Impact of mutations in FLT3, PTPN11 and RAS genes on the overall survival of pediatric B cell precursor acute lymphoblastic leukemia in Brazil.
We analyzed mutations in four genes (FLT3, KRAS/NRAS and PTPN11) that might disrupt the RAS/mitogen activated protein kinase (MAPKinase) signaling pathway, to evaluate their prognostic value in children younger than 16 years old with B-cell precursor acute lymphoblastic leukemia (Bcp-ALL). The overall survival (OS) was determined with the Kaplan-Meier method. MAPKinase genes were mutated in 25.4% and 20.1% of childhood and infant Bcp-ALL, respectively. Children with hyperdiploidy were more prone to harboring a MAPKinase gene mutation (odds ratio [OR] 3.18; 95% confidence interval [CI] 1.07-9.49). The mean OS of all cases was 54.0 months. FLT3 and PTPN11 mutations had no impact on OS. K/NRAS mutations were strongly associated with MLL-AFF1 (OR 5.78; 95% CI 1.00-33.24), and conferred poorer OS (p = 0.034) in univariate analysis.
Pediatric Hematology and Oncology Program, Research Center, Instituto Nacional de Câncer , Rio de Janeiro , Brazil.
Thayana Conceição
TC
Barbosa
Francianne Gomes
FG
Andrade
Bruno Almeida
BA
Lopes
Camilla Fernanda Gomes
CF
de Andrade
Marcela Braga
MB
Mansur
Mariana
M
Emerenciano
Maria S
MS
Pombo-de-Oliveira
D001938:Brazil; D002648:Child; D002675:Child, Preschool; D005260:Female; D011905:Genes, ras; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D016017:Odds Ratio; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D011379:Prognosis; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics*; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
D015514:Oncogene Proteins, Fusion; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11
Acute lymphoblastic leukemia; FLT3; K/NRAS; PTPN11; prognosis