Research publications

Found 4 publicacions matching the indicated search criteria.
Saumell S, Fernández-Serrano M, Mesa A, López-Cadenas F, Arenillas L, Alfonso A, Montoro MJ, Molero A, Leoz P, Riego V, Gallur L, Salamero O, Navarrete M, Tazón-Vega B, Ortega M, Reig Ò, Roué G, Calvo X, Prosper F, Díez-Campelo M, Valcárcel D

Prognostic impact of micromegakaryocytes in primary myelodysplastic syndromes.

Leuk Lymphoma May 2022, 63 (5) 1227-1235. Epub 31 Dec 2021
Micromegakaryocytes (microMKs) are considered a myelodysplastic feature of myeloid neoplasms in adults, with an adverse prognosis connotation. However, this notion in MDS has not been well proved. In our cohort of 287 MDS, patients with microMKs showed lower overall survival (OS) (HR, 2.12; 95% CI, 1.47-3.06;
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Fernández-Serrano M, Winkler R, Santos JC, Le Pannérer MM, Buschbeck M, Roué G

Histone Modifications and Their Targeting in Lymphoid Malignancies.

Int J Mol Sci 27 Dec 2021, 23 (1) . Epub 27 Dec 2021
In a wide range of lymphoid neoplasms, the process of malignant transformation is associated with somatic mutations in B cells that affect the epigenetic machinery. Consequential alterations in histone modifications contribute to disease-specific changes in the transcriptional program. Affected genes commonly play important roles in cell cycle regulation, apoptosis-inducing signal transduction, and DNA damage response, thus facilitating the emergence of malignant traits that impair immune surveillance and favor the emergence of different B-cell lymphoma subtypes. In the last two decades, the field has made a major effort to develop therapies that target these epigenetic alterations. In this review, we discuss which epigenetic alterations occur in B-cell non-Hodgkin lymphoma. Furthermore, we aim to present in a close to comprehensive manner the current state-of-the-art in the preclinical and clinical development of epigenetic drugs. We focus on therapeutic strategies interfering with histone methylation and acetylation as these are most advanced in being deployed from the bench-to-bedside and have the greatest potential to improve the prognosis of lymphoma patients.
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Marc Armengol, Juliana Carvalho Santos, Miranda Fernández-Serrano, Núria Profitós-Pelejà, Marcelo Lima Ribeiro, Gaël Roué

Immune-Checkpoint Inhibitors in B-Cell Lymphoma

Cancers 2021, 13(2), 214 8 Jan 2021, .
For years, immunotherapy has been considered a viable and attractive treatment option for patients with cancer. Among the immunotherapy arsenal, the targeting of intratumoral immune cells by immune-checkpoint inhibitory agents has recently revolutionised the treatment of several subtypes of tumours. These approaches, aimed at restoring an effective antitumour immunity, rapidly reached the market thanks to the simultaneous identification of inhibitory signals that dampen an effective antitumor response in a large variety of neoplastic cells and the clinical development of monoclonal antibodies targeting checkpoint receptors. Leading therapies in solid tumours are mainly focused on the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1) pathways. These approaches have found a promising testing ground in both Hodgkin lymphoma and non-Hodgkin lymphoma, mainly because, in these diseases, the malignant cells interact with the immune system and commonly provide signals that regulate immune function. Although several trials have already demonstrated evidence of therapeutic activity with some checkpoint inhibitors in lymphoma, many of the immunologic lessons learned from solid tumours may not directly translate to lymphoid malignancies. In this sense, the mechanisms of effective antitumor responses are different between the different lymphoma subtypes, while the reasons for this substantial difference remain partially unknown. This review will discuss the current advances of immune-checkpoint blockade therapies in B-cell lymphoma and build a projection of how the field may evolve in the near future. In particular, we will analyse the current strategies being evaluated both preclinically and clinically, with the aim of fostering the use of immune-checkpoint inhibitors in lymphoma, including combination approaches with chemotherapeutics, biological agents and/or different immunologic therapies.
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Ribeiro ML, Reyes-Garau D, Armengol M, Fernández-Serrano M, Roué G

Recent Advances in the Targeting of Epigenetic Regulators in B-Cell Non-Hodgkin Lymphoma.

Front Genet 2019, 10 986. Epub 16 Oct 2019
In the last 10 years, major advances have been made in the diagnosis and development of selective therapies for several blood cancers, including B-cell non-Hodgkin lymphoma (B-NHL), a heterogeneous group of malignancies arising from the mature B lymphocyte compartment. However, most of these entities remain incurable and current treatments are associated with variable efficacy, several adverse events, and frequent relapses. Thus, new diagnostic paradigms and novel therapeutic options are required to improve the prognosis of patients with B-NHL. With the recent deciphering of the mutational landscapes of B-cell disorders by high-throughput sequencing, it came out that different epigenetic deregulations might drive and/or promote B lymphomagenesis. Consistently, over the last decade, numerous epigenetic drugs (or epidrugs) have emerged in the clinical management of B-NHL patients. In this review, we will present an overview of the most relevant epidrugs tested and/or used so far for the treatment of different subtypes of B-NHL, from first-generation epigenetic therapies like histone acetyl transferases (HDACs) or DNA-methyl transferases (DNMTs) inhibitors to new agents showing selectivity for proteins that are mutated, translocated, and/or overexpressed in these diseases, including EZH2, BET, and PRMT. We will dissect the mechanisms of action of these epigenetic inhibitors, as well as the molecular processes underlying their lack of efficacy in refractory patients. This review will also provide a summary of the latest strategies being employed in preclinical and clinical settings, and will point out the most promising lines of investigation in the field.
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