Artículos de revista DCIE - ZIES Aldizkari artikuluak

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Browsing Artículos de revista DCIE - ZIES Aldizkari artikuluak by Author "Agirre, Xabier"

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    PublicationOpen Access
    Down-regulation of EVI1 is associated with epigenetic alterations and good prognosis in patients with acute myeloid leukemia
    (Ferrata Storti Foundation, 2012-10-18) Vázquez Urio, Iria; Maicas, Miren; Cervera, José; Agirre, Xabier; Marin-Béjar, Oskar; Marcotegui, Nerea; Vicente, Carmen; Lahortiga, Idoya; Gómez-Benito, María; Carranza, Claudia; Valencia, Ana; Brunet, Salut; Lumbreras, Eva; Prósper, Felipe; Gómez-Casares, Teresa; Hernández-Rivas, Jesús M.; Calasanz, María José; Sanz, Miguel A.; Sierra, Jorge; Odero, María D.; Ciencias; Zientziak; Gobierno de Navarra / Nafarroako Gobernua
    Background The EVI1 gene (3q26) codes for a zinc finger transcription factor with important roles in both mammalian development and leukemogenesis. Over-expression of EVI1 through either 3q26 rearrangements, MLL fusions, or other unknown mechanisms confers a poor prognosis in acute myeloid leukemia. Design and Methods We analyzed the prevalence and prognostic impact of EVI1 over-expression in a series of 476 patients with acute myeloid leukemia, and investigated the epigenetic modifications of the EVI1 locus which could be involved in the transcriptional regulation of this gene. Results Our data provide further evidence that EVI1 over-expression is a poor prognostic marker in acute myeloid leukemia patients less than 65 years old. Moreover, we found that patients with no basal expression of EVI1 had a better prognosis than patients with expression/over-expression (P=0.036). We also showed that cell lines with over-expression of EVI1 had no DNA methylation in the promoter region of the EVI1 locus, and had marks of active histone modifications: H3 and H4 acetylation, and trimethylation of histone H3 lysine 4. Conversely, cell lines with no expression of EVI1 have DNA hypermethylation and are marked by repressive trimethylation of histone H3 lysine 27 at the EVI1 promoter. Conclusions Our results identify EVI1 over-expression as a poor prognostic marker in a large, independent cohort of acute myeloid leukemia patients less than 65 years old, and show that the total absence of EVI1 expression has a prognostic impact on the outcome of such patients. Furthermore, we demonstrated for the first time that an aberrant epigenetic pattern involving DNA methylation, H3 and H4 acetylation, and trimethylation of histone H3 lysine 4 and histone H3 lysine 27 might play a role in the transcriptional regulation of EVI1 in acute myeloid leukemia. This study opens new avenues for a better understanding of the regulation of EVI1 expression at a transcriptional level.
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    PublicationOpen Access
    NGS-based molecular karyotyping of multiple myeloma: results from the GEM12 clinical trial
    (MDPI, 2022-10-21) Rosa-Rosa, Juan Manuel; Cuenca, Isabel; Medina, Alejandro; Vázquez Urio, Iria; Sánchez-delaCruz, Andrea; Buenache, Natalia; Sánchez Pérez, Ricardo; Jiménez, Cristina; Rosiñol, Laura; Gutiérrez, Norma C.; Ruiz-Heredia, Yanira; Barrio Santiago; Oriol, Albert; Martín-Ramos, María-Luisa; Blanchard, María-Jesús; Ayala, Rosa; Ríos-Tamayo, Rafael; Sureda, Anna; Hernández, Miguel-Teodoro; Rubia, Javier de la; Alkorta Aranburu, Gorka; Agirre, Xabier; Bladé, Joan; Mateos, María-Victoria; Lahuerta, Juan-José; San-Miguel, Jesús F.; Calasanz, María José; García-Sanz, Ramón; Martínez-López, Joaquín; Ciencias; Zientziak
    Next-generation sequencing (NGS) has greatly improved our ability to detect the genomic aberrations occurring in multiple myeloma (MM); however, its transfer to routine clinical labs and its validation in clinical trials remains to be established. We designed a capture-based NGS targeted panel to identify, in a single assay, known genetic alterations for the prognostic stratification of MM. The NGS panel was designed for the simultaneous study of single nucleotide and copy number variations, insertions and deletions, chromosomal translocations and V(D)J rearrangements. The panel was validated using a cohort of 149 MM patients enrolled in the GEM2012MENOS65 clinical trial. The results showed great global accuracy, with positive and negative predictive values close to 90% when compared with available data from fluorescence in situ hybridization and whole-exome sequencing. While the treatments used in the clinical trial showed high efficacy, patients defined as high-risk by the panel had shorter progression-free survival (p = 0.0015). As expected, the mutational status of TP53 was significant in predicting patient outcomes (p = 0.021). The NGS panel also efficiently detected clonal IGH rearrangements in 81% of patients. In conclusion, molecular karyotyping using a targeted NGS panel can identify relevant prognostic chromosomal abnormalities and translocations for the clinical management of MM patients.
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    PublicationOpen Access
    Silencing of hsa-miR-124 by EVI1 in cell lines and patients with acute myeloid leukemia
    (National Academy of Sciences, 2010-01-07) Vázquez Urio, Iria; Maicas, Miren; Marcotegui, Nerea; Conchillo, Ana; Guruceaga, Elizabeth; Román-Gómez, José; Calasanz, María José; Agirre, Xabier; Prósper, Felipe; Odero, María D.; Ciencias; Zientziak
    We read with great interest the work published by Dickstein et al. (1) showing that induced EVI1 expression in a murine model silences miR-124 expression by DNA methylation. The EVI1 gene codes for a transcription factor implicated in the development and progression of high-risk acute myeloid leukemia (AML) (2, 3). We quantify the expression of 250 microRNAs (miRNAs; TaqManHuman miRNA assay set) in 15 myeloid cell lines. Statistical analysis comparing cell lines with and without EVI1 protein identified miRNAs differentially expressed (B > 0)