1. Mutations in TP53 and JAK2 are independent prognostic biomarkers in B-cell precursor acute lymphoblastic leukaemia
- Author
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Forero-Castro, Maribel, Robledo, Cristina, Benito Sánchez, Rocío, Bodega-Mayor, Irene, Rapado, Inmaculada, Hernández Rivas, Jesús María, Abáigar, María, Quijada-Alamo, Miguel, Sánchez-Pina, José M, Sala-Valdés, Mónica, Araujo-Silva, Fernanda, Kohlmann, Alexander, Fuster, José Luis, Arefi, Maryam, Heras, Natalia de las, Riesco, Susana, Rodríguez, Juan-Nicolás, Hermosín, Lourdes, Ribera, Jordi, Camos Guijosa, Mireia, Ramírez, Manuel, Díaz de Heredia Rubio, Cristina, Barragán, Eva, Martínez, Joaquín, Ribera, Jose M., and Fernández-Ruiz, Elena
- Subjects
JAK2 ,Next-generation sequencing (NGS) ,Mutation ,TP53 ,Acute lymphoblastic leukemia - Abstract
[EN]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, European Commision (EC). Funding FP7/SP1/HEALTH. Project Code: 306242
- Published
- 2017