Ibánez, MariamCarbonell Caballero, JoséSuch, EsperanzaGarcía Alonso, LuzLiguori, AlessandroLópez Pavía, MaríaLlop, MartaAlonso, CarmenBarragán, EvaGómez Seguí, InésNeef, AlexanderHervás, DavidMontesinos, PauSanz, GuillermoSanz, Miguel AngelDopazo, JoaquínCervera, José2020-11-172020-11-172018-10-10https://hdl.handle.net/2445/172138Acute myeloid leukemia (AML) is associated with the sequential accumulation of acquired genetic alterations. Although at diagnosis cytogenetic alterations are frequent in AML, roughly 50% of patients present an apparently normal karyotype (NK), leading to a highly heterogeneous prognosis. Due to this significant heterogeneity, it has been suggested that different molecular mechanisms may trigger the disease with diverse prognostic implications. We performed whole-exome sequencing (WES) of tumor-normal matched samples of de novo AML-NK patients lacking mutations in NPM1, CEBPA or FLT3-ITD to identify new gene mutations with potential prognostic and therapeutic relevance to patients with AML. Novel candidate-genes, together with others previously described, were targeted resequenced in an independent cohort of 100 de novo AML patients classified in the cytogenetic intermediate-risk (IR) category. A mean of 4.89 mutations per sample were detected in 73 genes, 35 of which were mutated in more than one patient. After a network enrichment analysis, we defined a single in silico model and established a set of seed-genes that may trigger leukemogenesis in patients with normal karyotype. The high heterogeneity of gene mutations observed in AML patients suggested that a specific alteration could not be as essential as the interaction of deregulated pathways.application/pdfengcc by (c) Ibáñez et al., 2018http://creativecommons.org/licenses/by/3.0/es/Leucèmia mieloideGenèticaMyeloid leukemiaGeneticsinfo:eu-repo/semantics/article2020-11-11info:eu-repo/semantics/openAccess30303964