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Berta Nieves Vázquez

Dra. Berta Nieves Vázquez: “Tener una beca Marie Skłodowska Curie es un paso clave hacia una posición estable como líder de grupo”

Para muchos investigadores, la movilidad es una forma de construir una carrera científica. Este fue el caso de Berta Nieves Vázquez que, después de doctorarse en la Universidad de Barcelona, ​​cruzó el océano para su primera experiencia postdoctoral en la Rutgers University, en New Jersey (EE. UU.). Siete años de investigación exitosa después, se encontró frente a una de las decisiones más difíciles, aunque habituales, de un investigador expatriado. Como dijo la banda británica The Clash en 1982: ¿should I stay, or should I go?

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Anna Bigas Top100

La Dra. Anna Bigas, entre las "Top 100 Mujeres Líderes"

La Vicedirectora de Investigación Preclínica del Instituto de Investigación Contra la Leucemia Josep Carreras y jefe del grupo de Células Madre y Cáncer, con sede en el campus Hospital del Mar - IMIM, ha sido seleccionada como una de las 100 mujeres líderes más destacadas de España.

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Manel Esteller 3

Descubrimiento de factores epigenéticos que predicen la gravedad de la enfermedad COVID-19

Un artículo publicado en la revista EBiomedicine por el grupo del Dr. Manel Esteller, Director del Instituto de Investigación contra la Leucemia Josep Carreras y la Dra. Aurora Pujol,  jefa del Grupo de Enfermedades Neurometabólicas del Instituto de Investigación Biomédica de Bellvitge (IDIBELL), demuestra que la dotación epigenética de cada persona influye en la severidad de la enfermedad COVID-19.

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PEMED 2021

El simposio de Medicina personalizada y de precisión PEMED 2021, presidido por el Instituto de Investigación contra la Leucemia Josep Carreras, debate el futuro de los tratamientos a medida

Científicos de renombre internacional en el campo de la medicina personalizada y de precisión se reúnen online en el simposio PEMED 2021, presidido por el Instituto de Investigación contra la Leucemia Josep Carreras, para compartir los últimos descubrimientos sobre cómo la variabilidad individual modifica los tratamientos disponibles para enfermedades complejas.

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CAR-T Sant Pau

Sant Pau administra el primer CAR-T de producción propia para linfoma de Hodgkin y no-Hodgkin T de Europa

El primer medicamento de inmunoterapia CAR-T producido  enteramente en Sant Pau (académico) y administrado al primer paciente forma parte de un ensayo clínico pionero en Europa de inmunoterapia CAR-T de fase I / II para el tratamiento autólogo del linfoma de Hodgkin clásico y linfoma no-Hodgkin T CD30 + en recidiva / refractario, financiado por el Instituto de Salud Carlos III y la Fundación Josep Carreras contra la Leucemia.  

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Ignacio Campillo-Marcosa, Damiana Alvarez-Errico, Regina A. Alandes, Elisabetta Mereu, Manel Esteller

Single-Cell Technologies and Analyses in Hematopoiesis and Hematological Malignancies

Experimental Hematology(2021), doi.org/10.1016/j.exphem.2021.05.001 9 May 2021, .
In recent years, single-cell technologies have emerged as breakthrough techniques that enable the characterization of hematopoietic cell populations of normal and malignant tissue samples and will be combined in the near future with bulk technologies, currently used in clinical practice, in order to improve diagnosis, prognosis and search for novel molecular targets. These single-cell methods have the advantage of not masking cell-to-cell variation features and involve the study of genetic, epigenetic, transcriptional and proteomic landscapes from a single-cell perspective. Latest advances in this field have enabled the development of novel strategies that significantly increase both sensitivity and high-throughput. In this review, we emphasize emerging techniques aimed at assessing individual or multi-omic parameters at single-cell resolution, and analyze how these technologies have helped us understand hematopoietic variability and identify unknown and/or rare subpopulations. We also summarize the impact of these single-cell profiling strategies on the characterization of cell diversity within the tumor, and the clonal evolution of multiple hematological malignancies in samples from untreated and treated patients, which provide valuable information for diagnosis, prognosis and future treatments, and explain why current therapies may fail. However, despite these improvements, new challenges lie ahead.
Palomo L, Acha P, Solé F

Genetic Aspects of Myelodysplastic/Myeloproliferative Neoplasms.

Cancers (Basel) 27 Abr 2021, 13 (9) .
Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are myeloid neoplasms characterized by the presentation of overlapping features from both myelodysplastic syndromes and myeloproliferative neoplasms. Although the classification of MDS/MPN relies largely on clinical features and peripheral blood and bone marrow morphology, studies have demonstrated that a large proportion of patients (~90%) with this disease harbor somatic mutations in a group of genes that are common across myeloid neoplasms. These mutations play a role in the clinical heterogeneity of these diseases and their clinical evolution. Nevertheless, none of them is specific to MDS/MPN and current diagnostic criteria do not include molecular data. Even when such alterations can be helpful for differential diagnosis, they should not be used alone as proof of neoplasia because some of these mutations may also occur in healthy older people. Here, we intend to review the main genetic findings across all MDS/MPN overlap syndromes and discuss their relevance in the management of the patients.
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Martínez-Gutiérrez A, Fernández-Duran I, Marazuela-Duque A, Simonet NG, Yousef I, Martínez-Rovira I, Martínez-Hoyos J, Vaquero A

Shikimic acid protects skin cells from UV-induced senescence through activation of the NAD+-dependent deacetylase SIRT1.

Aging (Albany NY) 26 Abr 2021, 13 .
UV radiation is one of the main contributors to skin photoaging by promoting the accumulation of cellular senescence, which in turn induces a proinflammatory and tissue-degrading state that favors skin aging. The members of the sirtuin family of NAD+-dependent enzymes play an anti-senescence role and their activation suggests a promising approach for preventing UV-induced senescence in the treatment of skin aging. A two-step screening designed to identify compounds able to protect cells from UV-induced senescence through sirtuin activation identified shikimic acid (SA), a metabolic intermediate in many organisms, as a bona-fide candidate. The protective effects of SA against senescence were dependent on specific activation of SIRT1 as the effect was abrogated by the SIRT1 inhibitor EX-527. Upon UV irradiation SA induced S-phase accumulation and a decrease in p16INK4A expression but did not protect against DNA damage or increased polyploidies. In contrast, SA reverted misfolded protein accumulation upon senescence, an effect that was abrogated by EX-527. Consistently, SA induced an increase in the levels of the chaperone BiP, resulting in a downregulation of unfolded protein response (UPR) signaling and UPR-dependent autophagy, avoiding their abnormal hyperactivation during senescence. SA did not directly activate SIRT1 in vitro, suggesting that SIRT1 is a downstream effector of SA signaling specifically in the response to cellular senescence. Our study not only uncovers a shikimic acid/SIRT1 signaling pathway that prevents cellular senescence, but also reinforces the role of sirtuins as key regulators of cell proteostasis.
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Fernández S, Palomo M, Molina P, Díaz-Ricart M, Escolar G, Tellez A, Seguí F, Ventosa H, Torramade-Moix S, Rovira M, Carreras E, Nicolás JM, Castro P

Progressive endothelial cell damage in correlation with sepsis severity. Defibrotide as a contender.

J Thromb Haemost 19 Abr 2021, .
Background: The vascular endothelium plays a key role in sepsis pathophysiology and the associated organ dysfunction. Methods: We evaluated endothelial function in an experimental in-vitro model of sepsis, using endothelial cells grown in the presence of serum from patients with septic syndromes (sepsis, severe sepsis, and septic shock), non-infectious systemic inflammatory response syndrome (NI-SIRS) and healthy volunteers. Experiments were performed in the absence and presence of defibrotide (DF) (100µg/mL) to evaluate its potential protective effect. Results: After exposure to patients' sera, there was a progressive endothelial cell activation in correlation with sepsis severity, with a proinflammatory and prothrombotic phenotype, exhibiting significantly increased expression of adhesion receptors at the surface (ICAM-1, p< 0.05 and VCAM-1, p< 0.05); higher production and release to the extracellular matrix (ECM) of Von Willebrand factor (p< 0.001); augmented thrombogenicity of the ECM towards platelets (p< 0.001); and increased phosphorylation of intracellular p38MAPK. DF prevented these changes in all groups. Conclusions: Markers of endothelial damage increased progressively in association with the severity of septic syndromes. The endothelium is therefore an important therapeutic target to prevent complications of sepsis. DF shows promising potential to modulate the endothelial damage associated with sepsis and may constitute a pharmacological tool to decrease its sequelae including multiorgan failure.
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Alessandro Liquori, Iván Lesende, Laura Palomo, Gayane Avetisyan, Mariam Ibáñez, Elisa González-Romero, Mireia Boluda-Navarro, Mireya Morote-Faubel, Cristian Garcia-Ruiz, Cristina Martinez-Valiente, Marta Santiago-Balsera, Inés Gomez-Seguí, Alejandra Sanjuan-Pla, Miguel A. Sanz, Guillermo Sanz, Francesc Solé, Esperanza Such, José Cervera

A Single-Run Next-Generation Sequencing (NGS) Assay for the Simultaneous Detection of Both Gene Mutations and Large Chromosomal Abnormalities in Patients with Myelodysplastic Syndromes (MDS) and Related Myeloid Neoplasms

Cancers 2021, 13(8), 1947 18 Abr 2021, .
Myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms are clonal disorders that share most of their cytogenetic and molecular alterations. Despite the increased knowledge of the prognostic importance of genetics in these malignancies, next-generation sequencing (NGS) has not been incorporated into clinical practice in a validated manner, and the conventional karyotype remains mandatory in the evaluation of suspected cases. However, non-informative cytogenetics might lead to an inadequate estimation of the prognostic risk. Here, we present a novel targeted NGS-based assay for the simultaneous detection of all the clinically relevant genetic alterations associated with these disorders. We validated this platform in a large cohort of patients by performing a one-to-one comparison with the lesions from karyotype and single-nucleotide polymorphism (SNP) arrays. Our strategy demonstrated an approximately 97% concordance with standard clinical assays, showing sensitivity at least equivalent to that of SNP arrays and higher than that of conventional cytogenetics. In addition, this NGS assay was able to identify both copy-neutral loss of heterozygosity events distributed genome-wide and copy number alterations, as well as somatic mutations within significant driver genes. In summary, we show a novel NGS platform that represents a significant improvement to current strategies in defining diagnosis and risk stratification of patients with MDS and myeloid-related disorders.

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