Portal de investigación
Mutations in TP53 and JAK2 are independent prognostic biomarkers in B-cell precursor acute lymphoblastic leukaemia
Fecha de publicación:
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Forero-Castro, M
- Robledo, C
- Benito, R
- Bodega-Mayor, I
- Rapado, I
- Hernandez-Sanchez, M
- Abaigar, M
- Maria Sanchez-Pina, Jose
- Sala-Valdes, M
- Kohlmann, A
- Luis Fuster, Jose
- Arefi, M
- de las Heras, N
- Riesco, S
- Rodriguez, JN
- Hermosin, L
- Ribera, J
- Camos Guijosa, Mireia
- Ramirez, M
- de Heredia Rubio, Cristina Diaz
- Martinez, J
- Ribera, JM
- Fernandez-Ruiz, E
- Hernandez-Rivas, JM
Grupos
Abstract
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 nextgeneration 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.
Datos de la publicación
- ISSN/ISSNe:
- 0007-0920, 1532-1827
- Tipo:
- Article
- Páginas:
- 256-265
- DOI:
- 10.1038/bjc.2017.152
- Factor de Impacto:
- 2,890 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
BRITISH JOURNAL OF CANCER NATURE PUBLISHING GROUP
Citas Recibidas en Web of Science: 28
Documentos
- No hay documentos
Filiaciones
Keywords
- acute lymphoblastic leukaemia (ALL); next-generation sequencing (NGS); prognosis; outcome; survival; TP53; JAK2; mutation
Proyectos asociados
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Cita
Forero M,Robledo C,Benito R,Bodega I,Rapado I,Hernandez M,Abaigar M,Maria Hernandez J,Quijada M,Maria Sanchez J,Sala M,Araujo F,Kohlmann A,Luis J,Arefi M,de las Heras N,Riesco S,Rodriguez JN,Hermosin L,Ribera J,Camos M,Ramirez M,de Heredia CD,Barragan E,Martinez J,Ribera JM,Fernandez E,Hernandez JM. Mutations in TP53 and JAK2 are independent prognostic biomarkers in B-cell precursor acute lymphoblastic leukaemia. Br J Cancer. 2017. 117. (2):p. 256-265. IF:5,922. (1).