Patients, doctors and researchers in an interdisciplinary and privileged environment

Patients, at the center of research

Research in to the basic, epidemiological, preventive, clinical and translational aspects of leukaemia and other hematologic malignancies

Caring research

2020 June 5

Complement and endothelium are key to understanding the development of thrombotic micronagiopathies.

The Barcelona Endothelium Team, led by Enric Carreras, publishes a case review linked to previous work to detect whether the cause of thrombotic microangiopathy in Multiple Myeloma patients treated with carfilzomib is due to activation of the complement pathway, a cause that can be inhibited with a drug already on the market.

2020 June 3

Scientific publishing production between April and June

Scientific editorial production continues despite the SARS-CoV-2, COVID-19 crisis. List of publications by researchers of the Josep Carreras Institute between April 7 and June 3, 2020.

2020 May 27

CAR-T cells against B-cell Acute Lymphoblastic Leukemia.

Experience of the research project "Innovative therapeutic strategies for mixed-lineage leukaemia: B-cell acute lymphoblastic leukaemia: InTheMLLrBALL", MSCA-IF 795833 by Samanta Romina Zanetti.

2020 May 26

Research with COVID19 and online scientific seminars set the starting point for de-escalation.

This week the Josep Carreras Institute begins its de-escalation, incorporating the increasing presence of its personnel and undertaking various initiatives for psychosocial adaptation, personal protection measures for workers, online scientific seminars, and adjustment of spaces and laboratories to work with coronavirus.

2020 May 21

Advances of the ID-VITRORED project

The Stem cell biology, developmental leukemia, and immunotherapy group, led by Pablo Menéndez, is participating in the ID-VITRORED project, which consists of adapting a technology to detect and identify anti-erythrocyte antibodies.

2020 May 18

The Proteomics Unit joins the COVID-19 Mass Spectrometry Coalition.

The Josep Carreras Institute Proteomics Unit joins the International Mass Spectrometry Coalition, which is working to provide molecular-level information of SARS-CoV-2 to accelerate diagnostics and treatment of COVID19 pandemic.

2020 May 13

First Epigenetic Study in 3D Human Cancer Cells

Manel Esteller performs the first massive epigenetic characterization in organoids or 3D cancer cultures and makes the data available to the research community to facilitate new findings on tumor development and progression.

Organoid image by Eduard Batlle Lab IRB Barcelona

2020 May 11

The Josep Carreras Leukaemia Research Institute participates in the MSCA RISE cONCReTE project.

The Institute joins the RISE Marie Sklodowska Curie Action (MSCA) cONCReTE project, Development of Cancer RNA Therapeutics. CONCReTe brings together nineteen research centers, universities, hospitals, and companies from nine countries to investigate safe and effective epigenetic therapies against cancer through the exchange of their scientific and technical staff.

2020 May 6

Manel Esteller participates in the Exceptional Responders to Cancer Treatments Initiative

The Josep Carreras Institute, with Manel Esteller as Group Leader, participates in the Exceptional Responders Initiative, a pilot study by the US National Cancer Institute, whose viability has been published in the Journal of the National Cancer Institute.

2020 May 5

Discovered the physiopathological mechanisms underlying the most common pediatric Leukemia.

Researchers from the Josep Carreras Institute unveil the mechanisms that lead to hyperdiploid Acute Lymphoblastic Leukemia, Hyper D-ALL, the most common pediatric B-cell Leukaemia.

Hyperdiploid B-ALL blast in mitosis with lagging chromosomes

Recent publications

Comes M, Batlle M, Ribera JM

Treatment adapted to pregnancy in a patient with Burkitt lymphoma.

Med Clin (Barc) 12 Jun 2020, 154 (11) 470-471. Epub 20 Jul 2019More information

Casas E, Vavouri T

Mechanisms of epigenetic inheritance of variable traits through the germline.

Reproduction Jun 2020, 159 (6) R251-R263. Epub 22 Apr 2020

During the past half century, evidence for inheritance of variable traits has accumulated from experiments in plants and animals and epidemiological studies in humans. Here, we summarize some of the reported cases of epigenetic inheritance and the proposed mechanisms involved in the transmission of non-genetic information between generations in plants, nematodes, flies and mammals. It has long been accepted that information is epigenetically inherited in plants. Although many questions regarding the underlying mechanisms remain to be answered, it is now evident that epigenetic mechanisms are also responsible for the transmission of phenotypes in animals. We highlight similarities and differences between models and species.

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Blasco M, Martínez-Roca A, Rodríguez-Lobato LG, Garcia-Herrera A, Rosiñol L, Castro P, Fernández S, Quintana LF, Cibeira MT, Bladé J, Fernández de Larrea C, Tovar N, Jimenez R, Poch E, Guillen E, Campistol JM, Carreras E, Diaz-Ricart M, Palomo M

Complement as the enabler of carfilzomib-induced thrombotic microangiopathy.

Br. J. Haematol. 29 May 2020, . Epub 29 May 2020

Carfilzomib has been associated with the development of thrombotic microangiopathy (TMA) in relapsed/refractory multiple myeloma patients, a severe disease with no currently available aetiological treatment. We evaluated the potential role of terminal complement pathway in four patients with carfilzomib-induced TMA. Membrane attack complex (C5b-9) deposition on endothelial cells in culture exposed to plasma from patients during the acute phase of the disease suggests complement overactivation as a mechanism of potential endothelial damage in three out of four patients. If confirmed in larger cohorts, C5b-9 evaluation will allow early identification of patients who could benefit from complement blockade and treatment monitoring.

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Cossío FP, Esteller M, Berdasco M

Towards a more precise therapy in cancer: Exploring epigenetic complexity.

Curr Opin Chem Biol 29 May 2020, 57 41-49. Epub 29 May 2020

A plethora of preclinical evidences suggests that pharmacological targeting of epigenetic dysregulation is a potent strategy to combat human diseases. Nevertheless, the implementation of epidrugs in clinical practice is very scarce and mainly limited to haematological malignancies. In this review, we discuss cutting-edge strategies to foster the chemical design, the biological rationale and the clinical trial development of epidrugs. Specifically, we focus on the development of dual hybrids to exploit multitargeting of key epigenetic molecules deregulated in cancer; the study of epigenetic-synthetic lethality interactions as a mechanism to address loss-of-function mutations, and the combination of epidrugs with other therapies such as immunotherapy to avoid acquired chemoresistance and increase therapy sensitivity. By exploring these challenges, among others, the field of epigenetic chemical biology will increase its potential for clinical benefit, and more effective strategies targeting the aberrant epigenome in cancer are likely to be developed both in haematological and solid tumours.

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Colli ML, Ramos-Rodríguez M, Nakayasu ES, Alvelos MI, Lopes M, Hill JLE, Turatsinze JV, Coomans de Brachène A, Russell MA, Raurell-Vila H, Castela A, Juan-Mateu J, Webb-Robertson BM, Krogvold L, Dahl-Jorgensen K, Marselli L, Marchetti P, Richardson SJ, Morgan NG, Metz TO, Pasquali L, Eizirik DL

An integrated multi-omics approach identifies the landscape of interferon-α-mediated responses of human pancreatic beta cells.

Nat Commun 22 May 2020, 11 (1) 2584. Epub 22 May 2020

Interferon-α (IFNα), a type I interferon, is expressed in the islets of type 1 diabetic individuals, and its expression and signaling are regulated by T1D genetic risk variants and viral infections associated with T1D. We presently characterize human beta cell responses to IFNα by combining ATAC-seq, RNA-seq and proteomics assays. The initial response to IFNα is characterized by chromatin remodeling, followed by changes in transcriptional and translational regulation. IFNα induces changes in alternative splicing (AS) and first exon usage, increasing the diversity of transcripts expressed by the beta cells. This, combined with changes observed on protein modification/degradation, ER stress and MHC class I, may expand antigens presented by beta cells to the immune system. Beta cells also up-regulate the checkpoint proteins PDL1 and HLA-E that may exert a protective role against the autoimmune assault. Data mining of the present multi-omics analysis identifies two compound classes that antagonize IFNα effects on human beta cells.

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