Conexiones de los Microdominios de Tetraspaninas con el citoesqueleto de actina y su función en los procesos de Migración y Sinapsis Inmune

Tesis doctoral inédita. Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología. Fecha de lectura: 16-07-201

El análisis proteómico del interactoma intracelular revela que las tetraspaninas modulan el repertorio de proteínas que forman parte de los exosomas de linfocitos T humanos

Comunicaciones a congreso

Biological and functional analysis of interactions among tetraspanin-associated proteins in human T lymphocites by high-throuchput methods using second generation proteomics techniques

Comunicaciones a congreso

Mutations in TP53 and JAK2 are independent prognostic biomarkers in B-cell precursor acute lymphoblastic leukaemia

[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<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.European Commision (EC). Funding FP7/SP1/HEALTH. Project Code: 30624

Building peace from below: challenges and opportunities for a different peace

Las paces construidas desde los territorios son resultado de la interacción entre los procesos de reconocimiento/alineamiento estatal, de la presencia de los actores violentos y de las dinámicas de autonomía local. Los capítulos que componen este libro amplían, profundizan y problematizan estos ejes. Cada capítulo aborda y ofrece un panorama muy rico de los modos como se construyen las paces locales. Con especial énfasis en el departamento del Tolima, este libro pretende contribuir a crear una narrativa frente a los discursos dominantes de la paz en Colombia y analiza los diversos modos en que las comunidades locales vienen creando otras concepciones y prácticas de paz. El recorrido muestra la necesidad de reconocer otras formas de construir la paz, más allá de las narrativas oficiales y de los arreglos institucionales centrados en la reincorporación, la reducción de la violencia y la reparación a víctimas. Las tensiones regionales que se analizan evidencian que, a pesar de las constricciones impuestas por los actores violentos e, incluso, por las políticas públicas, las organizaciones y comunidades han logrado construir múltiples propuestas que requieren entrar en diálogo entre sí, pero también con la academia, con los medios de comunicación, con activistas, con la sociedad colombiana y con la comunidad internacional.Peace built from the territories is the result of an interaction between state recognition/alignment processes, the presence of violent actors, and the dynamics of local autonomy. The chapters that make up this book broaden, deepen, and problematize these thematic axes. Each chapter addresses and offers a rich panorama of how local peace processes are created. Focusing on the department of Tolima, this book aims to create a narrative against the dominant discourses of peace in Colombia and analyzes the various ways in which local communities have been constructing other conceptions and practices of peace. The journey demonstrates the need to recognize other ways of building peace beyond the official narratives and institutional arrangements focused on reincorporation, violence reduction, and victim reparations. The regional tensions analyzed here show that, despite the constraints imposed by violent actors and public policies, organizations and communities have been able to create multiple proposals that require establishing a dialogue among them, as well as with the academia, the media, activists, Colombian society, and the international community

Mutations in TP53 and JAK2 are independent prognostic biomarkers in B-cell precursor acute lymphoblastic leukaemia

[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.This work was supported in part by a grant from the European Union’s Seventh Framework Programme (FP7/2007–2013) under Grant Agreement 306242-NGS-PTL, the Consejeria de Educacion, Junta de Castilla y León (HUS272U13, SA085U16 to JMHR and JCYL-EDU/346/2013 PhD scholarship to MHS), Fundación Castellano Leonesa de Hematología y Hemoterapia (FUCALHH 2013) to JMHR, Proyectos de Investigacion del SACYL, Spain (BIO/SA31/13 and BIO/SA10/14) to RB; The Instituto de Salud Carlos III from Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund (ISCIII-FEDER) ‘‘Una manera de hacer Europa’’ Spanish Cancer Network (RD12/0036/0069 and RD12/0036/0061 to JM) and FIS grants PI15/01471 to JMHR and PI15/00032 to EFR. Universidad Pedagogica y Tecnologica de Colombia—Vicerrectoría de Investigacion y Extension (Grupo de Investigacion en Ciencias Biomedicas UPTC—GICBUPTC, Escuela de Ciencias Biologicas) to MFC.Peer Reviewe