RESUMO
Copy number aberrations (CNAs) represent cooperating events in B-lineage acute lymphoblastic leukaemia (B-ALL); however, their clinical relevance across different age cohorts is unclear. We analysed the recurrent CNAs in 157 age-stratified B-ALL negative cases for recurrent rearrangements (B-NEG ALL), and their association with patients' clinico-biological features. We found that: (i) CDKN2A/RB1-deleted and EBF1-deleted adults had a shorter disease-free survival than those with wild-type, (ii) among the unfavourable markers, CDKN2A/RB1 deletions and K/NRAS mutations retained their impact in multivariate analysis, encouraging the evaluation of CDKN2A/RB1 deletions and RAS mutations in the diagnostic/prognostic workflow to refine ALL risk assessment.
Assuntos
Variações do Número de Cópias de DNA/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Adolescente , Adulto , Fatores Etários , Idoso , Criança , DNA de Neoplasias/genética , Feminino , GTP Fosfo-Hidrolases/genética , Deleção de Genes , Genes p16 , Marcadores Genéticos/genética , Humanos , Lactente , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Mutação , Proteínas de Neoplasias/genética , Prognóstico , Proteínas de Ligação a Retinoblastoma/genética , Análise de Sobrevida , Ubiquitina-Proteína Ligases/genética , Adulto JovemRESUMO
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.