2024-03-28T15:42:58Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1691432022-04-19T09:06:58Zcom_10261_112com_10261_1col_10261_365
http://hdl.handle.net/10261/169143
10.1038/bjc.2017.152
348862
Mutations in TP53 and JAK2 are independent prognostic biomarkers in B-cell precursor acute lymphoblastic leukaemia
Nature Publishing Group
2017
artículo
Forero-Castro, Maribel
Robledo, Cristina
Benito, Rocío
Bodega-Mayor, Irene
Rapado, Inmaculada
Hernández-Sánchez, María
Abáigar, María
Hernandez-Sánchez, Jesus M.
Quijada-Álamo, Miguel
Sánchez-Pina, José María
Sala-Valdés, Mónica
Araujo-Silva, Fernando
Kohlmann, Alexander
Fuster, José Luis
Arefi, Maryam
Heras, Natalia de las
Riesco, Susana
Rodríguez, Juan-Nicolas
Hermosín, Lourdes
Ribera, Jordi
Camos Guijosa, Mireia
Ramírez, Manuel
Díaz de Heredia, Cristina
Barragán, Eva
Martínez-López, Joaquín
Ribera, Josep-Maria
Fernández-Ruiz, Elena
Hernández, Jesús M.
rp08225
2017
[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.
Ministerio de Economía y Competitividad (España)
Instituto de Salud Carlos III
Red Temática de Investigación Cooperativa en Cáncer (España)
Universidad Pedagógica y Tecnológica de Colombia
Junta de Castilla y León
European Commission
British Journal of Cancer
2017
117
256
265