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[PMID]: | 28557976 |
[Au] Autor: | Forero-Castro M; Robledo C; Benito R; Bodega-Mayor I; Rapado I; Hernández-Sánchez M; Abáigar M; Maria Hernández-Sánchez J; Quijada-Álamo M; María Sánchez-Pina J; Sala-Valdés M; Araujo-Silva F; Kohlmann A; Luis Fuster J; Arefi M; de Las Heras N; Riesco S; Rodríguez JN; Hermosín L; Ribera J; Camos Guijosa M; Ramírez M; de Heredia Rubio CD; Barragán E; Martínez J; Ribera JM; Fernández-Ruiz E; Hernández-Rivas JM |
[Ad] Endereço: | IBSAL, IBMCC, University of Salamanca, CSIC, Cancer Research Center, Campus Miguel de Unamuno, Salamanca 37007, Spain. |
[Ti] Título: | Mutations in TP53 and JAK2 are independent prognostic biomarkers in B-cell precursor acute lymphoblastic leukaemia. |
[So] Source: | Br J Cancer;117(2):256-265, 2017 Jul 11. | [Is] ISSN: | 1532-1827 |
[Cp] País de publicação: | England |
[La] Idioma: | eng |
[Ab] Resumo: | BACKGROUND: In B-cell precursor acute lymphoblastic leukaemia (B-ALL), the identification of additional genetic alterations associated with poor prognosis is still of importance. We determined the frequency and prognostic impact of somatic mutations in children and adult cases with B-ALL treated with Spanish PETHEMA and SEHOP protocols. METHODS: Mutational status of hotspot regions of TP53, JAK2, PAX5, LEF1, CRLF2 and IL7R genes was determined by next-generation deep sequencing in 340 B-ALL patients (211 children and 129 adults). The associations between mutation status and clinicopathological features at the time of diagnosis, treatment outcome and survival were assessed. Univariate and multivariate survival analyses were performed to identify independent prognostic factors associated with overall survival (OS), event-free survival (EFS) and relapse rate (RR). RESULTS: A mutation rate of 12.4% was identified. The frequency of adult mutations was higher (20.2% vs 7.6%, P=0.001). TP53 was the most frequently mutated gene (4.1%), followed by JAK2 (3.8%), CRLF2 (2.9%), PAX5 (2.4%), LEF1 (0.6%) and IL7R (0.3%). All mutations were observed in B-ALL without ETV6-RUNX1 (P=0.047) or BCR-ABL1 fusions (P<0.0001). In children, TP53mut was associated with lower OS (5-year OS: 50% vs 86%, P=0.002) and EFS rates (5-year EFS: 50% vs 78.3%, P=0.009) and higher RR (5-year RR: 33.3% vs 18.6% P=0.037), and was independently associated with higher RR (hazard ratio (HR)=4.5; P=0.04). In adults, TP53mut was associated with a lower OS (5-year OS: 0% vs 43.3%, P=0.019) and a higher RR (5-year RR: 100% vs 61.4%, P=0.029), whereas JAK2mut was associated with a lower EFS (5-year EFS: 0% vs 30.6%, P=0.035) and a higher RR (5-year RR: 100% vs 60.4%, P=0.002). TP53mut was an independent risk factor for shorter OS (HR=2.3; P=0.035) and, together with JAK2mut, also were independent markers of poor prognosis for RR (TP53mut: HR=5.9; P=0.027 and JAK2mut: HR=5.6; P=0.036). CONCLUSIONS: TP53mut and JAK2mut are potential biomarkers associated with poor prognosis in B-ALL patients. |
[Mh] Termos MeSH primário: |
Biomarcadores Tumorais/genética Janus Quinase 2/genética Leucemia-Linfoma Linfoblástico de Células Precursoras/genética Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia Proteína Supressora de Tumor p53/genética
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[Mh] Termos MeSH secundário: |
Adolescente Adulto Idoso Idoso de 80 Anos ou mais Linfócitos B/patologia Criança Pré-Escolar Intervalo Livre de Doença Feminino Regulação Neoplásica da Expressão Gênica Sequenciamento de Nucleotídeos em Larga Escala Seres Humanos Lactente Masculino Meia-Idade Mutação Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia Prognóstico Receptores de Citocinas/biossíntese Resultado do Tratamento
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Biomarkers, Tumor); 0 (CRLF2 protein, human); 0 (Receptors, Cytokine); 0 (TP53 protein, human); 0 (Tumor Suppressor Protein p53); EC 2.7.10.2 (JAK2 protein, human); EC 2.7.10.2 (Janus Kinase 2) |
[Em] Mês de entrada: | 1708 |
[Cu] Atualização por classe: | 170817 |
[Lr] Data última revisão:
| 170817 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170531 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1038/bjc.2017.152 |
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