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Eduard Porta Entrevista

Eduard Porta: "El futuro de la Inteligencia Artificial en biomedicina es brillante"

El Dr. Eduard Porta, líder del grupo de investigación en Inmunogenómica del Cáncer del Instituto de Investigación contra la Leucemia Josep Carreras, ha participado en una iniciativa científica comunitaria para poner en contexto el valor de las predicciones de AlphaFold2, el algoritmo de Deep Mind, la empresa especializada en inteligencia artificial de Google, capaz de determinar la estructura tridimensional de todas las proteínas humanas conocidas. Las conclusiones se han publicado recientemente en la revista especializada Nature Structural Biology.

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Unoentrecienmil 2022

Unoentrecienmil otorga su 9ª Beca Anual para el desarrollo de una inmunoterapia contra una de las leucemias pediátricas de peor pronóstico

La Fundación Unoentrecienmil, que impulsa proyectos de investigación para la curación plena de la leucemia infantil, otorga hoy su 9ª Beca Anual de Investigación a la Doctora Clara Bueno del Instituto de Investigación contra la Leucemia Josep Carreras. Durante dos años, la doctora llevará a cabo su trabajo para desarrollar nuevas estrategias terapéuticas, algunas basadas en inmunoterapia, contra el antígeno NG2, relacionado con las recaídas de la Leucemia Linfoblástica Aguda de células B con alteraciones en el gen MLL, y mejorar así el índice de supervivencia de estos pacientes, ahora en un 35%.

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IJC Building white wall

El Instituto de Investigación Contra la Leucemia Josep Carreras estabiliza 21 plazas estructurales convirtiéndose en uno de los centros de investigación con mayor crecimiento de Catalunya

El Diario Oficial de la Generalitat de Catalunya acaba de publicar la resolución que estabiliza 21 plazas de las unidades de administración y servicios comunes del Instituto de Investigación contra la Leucemia Josep Carreras. Con esta estabilización, el Instituto de Investigación adopta un esquema de contratación indefinida, tal y como marca la última reforma laboral.

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Eduard Porta 2022

Las predicciones de la estructura 3D de las proteínas realizadas por una inteligencia artificial pueden revolucionar la investigación del cáncer y el descubrimiento de fármacos

Un grupo de investigadores entre los que se encuentra el Dr. Eduard Porta, líder del Grupo de Inmunogenómica del Cáncer del Instituto de Investigación contra la Leucemia Josep Carreras, acaba de publicar los resultados de su investigación sobre cómo aprovechar los resultados de AlphaFold2 en el mundo real. Este algoritmo, basado en la inteligencia artificial Deep Mind desarrollada por Google, permite predecir la estructura 3D de proteínas basándose simplemente en información genómica.

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Ballestar lab 2022

La vitamina C puede ser la clave para mejorar la eficacia de las terapias anticancerígenas basadas en células dendríticas

Investigadores del Laboratorio de Epigenética y Enfermedades Inmunes del Instituto de Investigación contra la Leucemia Josep Carreras han demostrado que la vitamina C mejora las propiedades inmunogénicas de las células dendríticas, in vitro. Los resultados, publicados recientemente, muestran que el tratamiento de las células con vitamina C conduce a una activación más constante de los genes implicados en la respuesta inmunitaria, principalmente a través de la desmetilación del ADN, un tipo de reprogramación epigenética. Este descubrimiento puede ser útil para generar terapias basadas en células dendríticas más potentes en el futuro.

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CarrerasLeaders

CarrerasLeaders: el programa postdoctoral que capacita a futuros líderes para luchar contra los cánceres de la sangre

El Instituto de Investigación contra la Leucemia Josep Carreras (IJC) presenta CarrerasLeaders, un nuevo programa postdoctoral innovador e internacional que cuenta con la financiación del Programa Horizon Europe Marie Curie Skodowska COFUND (GA No. 101081347) de la Comisión Europea y cuenta con la colaboración de la Fundación Internacional Josep Carreras y la coordinación científica del Dr. Buschbeck.

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Manel Esteller WOS

Dr. Manel Esteller, director del Instituto de Investigación contra la Leucemia Josep Carreras, considerado entre los investigadores más relevantes a nivel mundial por sus hallazgos según la Universidad Stanford en Estados Unidos

Manel Esteller, Director del Instituto de Investigación contra la Leucemia Josep Carreras, es reconocido en el grupo del 0.06% de los investigadores con más impacto a nivel mundial en todas las áreas de la Ciencia por la prestigiosa Universidad Stanford en Estados Unidos.

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El Instituto de Investigación contra la Leucemia Josep Carreras abre un nuevo laboratorio para estudiar la organización del núcleo celular en la Leucemia

El Dr. Gregoire Stik se une al Instituto de Investigación contra la Leucemia Josep Carreras para dirigir el laboratorio de Organización de la cromatina en la Leucemia, que tiene como objetivo principal comprender los mecanismos moleculares que inducen y controlan la malignidad de las células leucémicas para encontrar nuevas dianas terapéuticas para el tratamiento de las neoplasias malignas linfoides. 

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Últimas publicaciones

Pamela Acha, Mar Mallo, Francesc Solé

Myelodysplastic Syndromes with Isolated del(5q): Value of Molecular Alterations for Diagnostic and Prognostic Assessment

Cancers 10 Nov 2022, .
Myelodysplastic syndromes (MDS) are a group of clonal hematological neoplasms characterized by ineffective hematopoiesis in one or more bone marrow cell lineages. Consequently, patients present with variable degrees of cytopenia and dysplasia. These characteristics constitute the basis for the World Health Organization (WHO) classification criteria of MDS, among other parameters, for the current prognostic scoring system. Although nearly half of newly diagnosed patients present a cytogenetic alteration, and almost 90% of them harbor at least one somatic mutation, MDS with isolated del(5q) constitutes the only subtype clearly defined by a cytogenetic alteration. The results of several clinical studies and the advances of new technologies have allowed a better understanding of the biological basis of this disease. Therefore, since the first report of the “5q- syndrome” in 1974, changes and refinements have been made in the definition and the characteristics of the patients with MDS and del(5q). Moreover, specific genetic alterations have been found to be associated with the prognosis and response to treatments. The aim of this review is to summarize the current knowledge of the molecular background of MDS with isolated del(5q), focusing on the clinical and prognostic relevance of cytogenetic alterations and somatic mutations.
Mehmet Akdel, Douglas E. V. Pires, Eduard Porta Pardo, Jürgen Jänes, Arthur O. Zalevsky, Bálint Mészáros, Patrick Bryant, Lydia L. Good, Roman A. Laskowski, Gabriele Pozzati, Aditi Shenoy, Wensi Zhu, Petras Kundrotas, Victoria Ruiz Serra, Carlos H. M. Rodrigues, Alistair S. Dunham, David Burke, Neera Borkakoti, Sameer Velankar, Adam Frost, Jérôme Basquin, Kresten Lindorff-Larsen, Alex Bateman, Andrey V. Kajava, Alfonso Valencia, Sergey Ovchinnikov, Janani Durairaj, David B. Ascher, Janet M. Thornton, Norman E. Davey, Amelie Stein, Arne Elofsson, Tristan I. Croll & Pedro Beltrao

A structural biology community assessment of AlphaFold2 applications

Nature Structural & Molecular Biology 7 Nov 2022, .
Most proteins fold into 3D structures that determine how they function and orchestrate the biological processes of the cell. Recent developments in computational methods for protein structure predictions have reached the accuracy of experimentally determined models. Although this has been independently verified, the implementation of these methods across structural-biology applications remains to be tested. Here, we evaluate the use of AlphaFold2 (AF2) predictions in the study of characteristic structural elements; the impact of missense variants; function and ligand binding site predictions; modeling of interactions; and modeling of experimental structural data. For 11 proteomes, an average of 25% additional residues can be confidently modeled when compared with homology modeling, identifying structural features rarely seen in the Protein Data Bank. AF2-based predictions of protein disorder and complexes surpass dedicated tools, and AF2 models can be used across diverse applications equally well compared with experimentally determined structures, when the confidence metrics are critically considered. In summary, we find that these advances are likely to have a transformative impact in structural biology and broader life-science research.
González-Gil C, Morgades M, Lopes T, Fuster-Tormo F, García-Chica J, Zhao R, Montesinos P, Torrent A, Diaz-Beya M, Coll R, Hermosín L, Mercadal S, González-Campos J, Zamora L, Artola T, Vall-Llovera F, Tormo M, Gil-Cortés C, Barba P, Novo A, Ribera J, Bernal T, De Ugarriza PL, Queipo MP, Martínez-Sánchez P, Giménez A, González-Martínez T, Cladera A, Cervera J, Fernández-Martín R, Ardaiz MÁ, Vidal MJ, Baena Á, López-Bigas N, Bigas A, Maciejewski J, Orfao A, Ribera JM, Genescà E

Genomics improves risk stratification of adults with T-cell acute lymphoblastic leukemia patients enrolled in measurable residual disease-oriented trials.

Haematologica 3 Nov 2022, . Epub 3 Nov 2022
Genetic information has been crucial to understand the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL) at diagnosis and at relapse, but still nowadays has a limited value in a clinical context. Few genetic markers are associated with the outcome of T-ALL patients, independently of measurable residual disease (MRD) status after therapy. In addition, the prognostic relevance of genetic features may be modulated by the specific treatment used. We analyzed the genetic profile of 145 T-ALL patients by targeted deep sequencing. Genomic information was integrated with the clinical-biological and survival data of a subset of 116 adult patients enrolled in two consecutive MRD-oriented trials of the Spanish PETHEMA (Programa Español de Tratamientos en Hematología) group. Genetic analysis revealed a mutational profile defined by DNMT3A/ N/KRAS/ MSH2/ U2AF1 gene mutations that identified refractory/resistant patients. Mutations in the DMNT3A gene were also found in the nonleukemic cell fraction of patients with T-ALL, revealing a possible mutational-driven clonal hematopoiesis event to prime T-ALL in elderly. The prognostic impact of this adverse genetic profile was independent of MRD status on day +35 of induction therapy. The combined WOG signature and MRD on day +35 allowed risk-stratification of T-ALL into standard or high-risk groups with significantly different 5-year overall survival (OS) (95% confidence interval [CI]) of 52% (37-67 %) and 17% (1-33%), respectively. These results confirm the relevance of the tumor genetic profile in predicting patient outcome in adult T-ALL and highlight the need for novel gene-targeted chemotherapeutic schedules to improve the OS of poor-prognosis T-ALL patients.
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Marguerite-Marie Le Pannérer, Jeannine Diesch, Raquel Casquero, Michael Maher, Olga Garcia, Torsten Haferlach, Johannes Zuber, Andrea Kündgen, Katharina Götze, Marcus Buschbeck

Different Gene Sets Are Associated With Azacitidine Response In Vitro Versus in Myelodysplastic Syndrome Patients

HemaSphere 1 Nov 2022, 6 (11) .
Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic disorders characterized by dysplasia, ineffective hematopoiesis, and predisposition to secondary acute myeloid leukemias (sAML). Azacitidine (AZA) is the standard care for high-risk MDS patients not eligible for allogenic bone marrow transplantation. However, only half of the patients respond to AZA and eventually all patients relapse. Response-predicting biomarkers and combinatorial drugs targets enhancing therapy response and its duration are needed. Here, we have taken a dual approach. First, we have evaluated genes encoding chromatin regulators for their capacity to modulate AZA response. We were able to validate several genes, whose genetic inhibition affected the cellular AZA response, including 4 genes encoding components of Imitation SWItch chromatin remodeling complex pointing toward a specific function and co-vulnerability. Second, we have used a classical cohort analysis approach measuring the expression of a gene panel in bone marrow samples from 36 MDS patients subsequently receiving AZA. The gene panel included the identified AZA modulators, genes known to be involved in AZA metabolism and previously identified candidate modulators. In addition to confirming a number of previously made observations, we were able to identify several new associations, such as NSUN3 that correlated with increased overall survival. Taken together, we have identified a number of genes associated with AZA response in vitro and in patients. These groups of genes are largely nonoverlapping suggesting that different gene sets need to be exploited for the development of combinatorial drug targets and response-predicting biomarkers.
Morante-Palacios O, Godoy-Tena G, Calafell-Segura J, Ciudad L, Martínez-Cáceres EM, Sardina JL, Ballestar E

Vitamin C enhances NF-κB-driven epigenomic reprogramming and boosts the immunogenic properties of dendritic cells.

Nucleic Acids Res 28 Oct 2022, . Epub 28 Oct 2022
Dendritic cells (DCs), the most potent antigen-presenting cells, are necessary for effective activation of naïve T cells. DCs' immunological properties are modulated in response to various stimuli. Active DNA demethylation is crucial for DC differentiation and function. Vitamin C, a known cofactor of ten-eleven translocation (TET) enzymes, drives active demethylation. Vitamin C has recently emerged as a promising adjuvant for several types of cancer; however, its effects on human immune cells are poorly understood. In this study, we investigate the epigenomic and transcriptomic reprogramming orchestrated by vitamin C in monocyte-derived DC differentiation and maturation. Vitamin C triggers extensive demethylation at NF-κB/p65 binding sites, together with concordant upregulation of antigen-presentation and immune response-related genes during DC maturation. p65 interacts with TET2 and mediates the aforementioned vitamin C-mediated changes, as demonstrated by pharmacological inhibition. Moreover, vitamin C increases TNFβ production in DCs through NF-κB, in concordance with the upregulation of its coding gene and the demethylation of adjacent CpGs. Finally, vitamin C enhances DC's ability to stimulate the proliferation of autologous antigen-specific T cells. We propose that vitamin C could potentially improve monocyte-derived DC-based cell therapies.
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