Forero-Castro, MaribelRobledo, CristinaBenito, RocíoBodega-Mayor, IreneRapado, InmaculadaHernández-Sánchez, MaríaAbáigar, MaríaMaria Hernández-Sánchez, JesúsQuijada-Álamo, MiguelMaría Sánchez-Pina, JoséSala-Valdés, MónicaAraujo-Silva, FernandaKohlmann, AlexanderLuis Fuster, JoséArefi, Maryamde Las Heras, NataliaRiesco, SusanaRodríguez, Juan NHermosín, LourdesRibera, JordiCamos Guijosa, MireiaRamírez, Manuelde Heredia Rubio, Cristina DíazBarragán, EvaMartínez, JoaquínRibera, José MFernández-Ruiz, ElenaHernández-Rivas, Jesús-María2023-01-252023-01-252017-05-30http://hdl.handle.net/10668/11250In 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. 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). 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 TP53mut and JAK2mut are potential biomarkers associated with poor prognosis in B-ALL patients.enAttribution-NonCommercial-ShareAlike 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-sa/4.0/AdolescentAdultAgedAged, 80 and overB-LymphocytesBiomarkers, TumorChildChild, PreschoolDisease-Free SurvivalFemaleGene Expression Regulation, NeoplasticHigh-Throughput Nucleotide SequencingHumansInfantJanus Kinase 2MaleMiddle AgedMutationPrecursor Cell Lymphoblastic Leukemia-LymphomaPrognosisReceptors, CytokineTreatment OutcomeTumor Suppressor Protein p53research article28557976open access10.1038/bjc.2017.1521532-1827PMC5520505https://www.nature.com/articles/bjc2017152.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520505/pdf