Publicació científica

S'han trobat 1373 publicacions amb els criteris indicats.
Adema V, Palomo L, Toma A, Kosmider O, Fuster-Tormo F, Benito R, Salgado R, Such E, Larrayoz MJ, Xicoy B, Hernandez-Sanchez JM, Maietta P, Neef A, Fontenay M, Ibañez M, Diez-Campelo M, Alvarez S, Maciejewski JP, Fenaux P, Sole F

Distinct mutational pattern of myelodysplastic syndromes with and without 5q- treated with lenalidomide.

Br. J. Haematol. 9 Mar 2020, . Epub 9 Mar 2020Més informació
Fernández-Sanlés A, Sayols-Baixeras S, Castro DE Moura M, Esteller M, Subirana I, Torres-Cuevas S, Pérez-Fernández S, Aslibekyan S, Marrugat J, Elosua R

Physical Activity and Genome-wide DNA Methylation: The REgistre GIroní del COR Study.

Med Sci Sports Exerc Mar 2020, 52 (3) 589-597.
DNA methylation may be one of the biological mechanisms underlying the health benefits of physical activity (PA). Our objective was to determine the association between PA and genome-wide DNA methylation at CpG level.
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de Barrios O, Meler A, Parra M

MYC's Fine Line Between B Cell Development and Malignancy.

Cells 24 Feb 2020, 9 (2) . Epub 24 Feb 2020
The transcription factor MYC is transiently expressed during B lymphocyte development, and its correct modulation is essential in defined developmental transitions. Although temporary downregulation of MYC is essential at specific points, basal levels of expression are maintained, and its protein levels are not completely silenced until the B cell becomes fully differentiated into a plasma cell or a memory B cell. MYC has been described as a proto-oncogene that is closely involved in many cancers, including leukemia and lymphoma. Aberrant expression of MYC protein in these hematological malignancies results in an uncontrolled rate of proliferation and, thereby, a blockade of the differentiation process. MYC is not activated by mutations in the coding sequence, and, as reviewed here, its overexpression in leukemia and lymphoma is mainly caused by gene amplification, chromosomal translocations, and aberrant regulation of its transcription. This review provides a thorough overview of the role of MYC in the developmental steps of B cells, and of how it performs its essential function in an oncogenic context, highlighting the importance of appropriate MYC regulation circuitry.
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Parra M, Baptista MJ, Genescà E, Llinàs-Arias P, Esteller M

Genetics and Epigenetics of Leukemia and Lymphoma: From Knowledge to Applications, Meeting Report of the Josep Carreras Leukaemia Research Institute.

Hematol Oncol 19 Feb 2020, . Epub 19 Feb 2020
The meeting, which brought together leading scientists and clinicians in the field of leukemia and lymphoma, was held at the new headquarters of the Josep Carreras Leukaemia Research Institute (IJC) in Badalona, Catalonia, Spain, September 19-20, 2019. Its purpose was to highlight the latest advances in our understanding of the molecular mechanisms driving blood cancers, and to discuss how this knowledge can be translated into an improved management of the disease. Special emphasis was placed on the role of genetic and epigenetic heterogeneity, and the exploitation of epigenetic regulation for developing biomarkers and novel treatment approaches. This article is protected by copyright. All rights reserved.
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Crisà E, Kulasekararaj AG, Adema V, Such E, Schanz J, Haase D, Shirneshan K, Best S, Mian SA, Kizilors A, Cervera J, Lea N, Ferrero D, Germing U, Hildebrandt B, Martínez ABV, Santini V, Sanz GF, Solé F, Mufti GJ

Impact of somatic mutations in myelodysplastic patients with isolated partial or total loss of chromosome 7.

Leukemia 17 Feb 2020, . Epub 17 Feb 2020
Monosomy 7 [-7] and/or partial loss of chromosome 7 [del(7q)] are associated with poor and intermediate prognosis, respectively, in myelodysplastic syndromes (MDS), but somatic mutations may also play a key complementary role. We analyzed the impact on the outcomes of deep targeted mutational screening in 280 MDS patients with -7/del(7q) as isolated cytogenetic abnormality (86 with del(7q) and 194 with -7). Patients with del(7q) or -7 had similar demographic and disease-related characteristics. Somatic mutations were detected in 79% (93/117) of patients (82% in -7 and 73% in del(7q) group). Median number of mutations per patient was 2 (range 0-8). There was no difference in mutation frequency between the two groups. Patients harbouring ≥2 mutations had a worse outcome than patients with <2 or no mutations (leukaemic transformation at 24 months, 38% and 20%, respectively, p = 0.044). Untreated patients with del(7q) had better overall survival (OS) compared with -7 (median OS, 34 vs 17 months, p = 0.034). In multivariable analysis, blast count, TP53 mutations and number of mutations were independent predictors of OS, whereas the cytogenetic subgroups did not retain prognostic relevance. This study highlights the importance of mutational analysis in terms of prognosis in MDS patients with isolated -7 or del(7q).
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Capdevila J, Arqués O, Hernández Mora JR, Matito J, Caratù G, Mancuso FM, Landolfi S, Barriuso J, Jimenez-Fonseca P, Lopez Lopez C, Garcia-Carbonero R, Hernando J, Matos I, Paolo N, Hernández-Losa J, Esteller M, Martínez-Cardús A, Tabernero J, Vivancos A, Palmer HG

Epigenetic EGFR Gene Repression Confers Sensitivity to Therapeutic BRAFV600E Blockade in Colon Neuroendocrine Carcinomas

Clin. Cancer Res. 15 Feb 2020, 26 (4) 902-909. Epub 31 Oct 2019
The limited knowledge of the molecular alterations that characterize poorly differentiated neuroendocrine carcinomas has limited the clinical development of targeted agents directed to driver mutations. Here we aim to identify new molecular targets in colon neuroendocrine carcinomas (co-NEC) and proof the efficacy of matching drugs.
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Esteve-Puig R, Bueno-Costa A, Esteller M

Writers, Readers and Erasers of RNA Modifications in Cancer.

Cancer Lett. 25 Gen 2020, . Epub 25 Gen 2020
Although cancer was originally considered a disease driven only by genetic mutations, it has now been proven that it is also an epigenetic disease driven by DNA hypermethylation-associated silencing of tumor suppressor genes and aberrant histone modifications. Very recently, a third component has emerged: the so-called epitranscriptome understood as the chemical modifications of RNA that regulate and alter the activity of RNA molecules. In this regard, the study of genetic and epigenetic disruption of the RNA-modifying proteins is gaining momentum in advancing our understanding of cancer biology. Furthermore, the development of epitranscriptomic anticancer drugs could lead to new promising and unexpected therapeutic strategies for oncology in the coming years.
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Ikemori R, Gabasa M, Duch P, Vizoso M, Bragado P, Arshakyan M, Luis IC, Marín A, Morán S, Castro M, Fuster G, Gea-Sorli S, Jauset T, Soucek L, Montuenga LM, Esteller M, Monsó E, Peinado VI, Gascon P, Fillat C, Hilberg F, Reguart N, Alcaraz J

Epigenetic SMAD3 repression in tumor-associated fibroblasts impairs fibrosis and response to the antifibrotic drug nintedanib in lung squamous cell carcinoma

Cancer Res. 15 Gen 2020, 80 (2) 276-290. Epub 6 Nov 2019
The tumor-promoting fibrotic stroma rich in tumor-associated fibroblasts (TAF) is drawing increased therapeutic attention. Intriguingly, a trial with the antifibrotic drug nintedanib in non-small cell lung cancer reported clinical benefits in adenocarcinoma (ADC) but not squamous cell carcinoma (SCC), even though the stroma is fibrotic in both histotypes. Likewise, we reported that nintedanib inhibited the tumor-promoting fibrotic phenotype of TAFs selectively in ADC. Here we show that tumor fibrosis is actually higher in ADC-TAFs than SCC-TAFs
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Perez-Amill L, Suñe G, Antoñana-Vildosola A, Castella M, Najjar A, Bonet J, Fernández-Fuentes N, Inogés S, López A, Bueno C, Juan M, Urbano-Ispizua A, Martín-Antonio B

Preclinical development of a humanized chimeric antigen receptor against B cell maturation antigen for multiple myeloma.

Haematologica 9 Gen 2020, . Epub 9 Gen 2020
Multiple myeloma is a prevalent and incurable disease, despite the development of new and effective drugs. The recent development of chimeric antigen receptor (CAR)-T cell therapy has shown impressive results in the treatment of patients with relapsed or refractory hematological B cell malignancies. In the recent years, B-cell maturation antigen (BCMA) has appeared as a promising antigen to target using a variety of immuno-therapy treatments including CART cells, for MM patients. To this end, we generated clinical-grade murine CART cells directed against BCMA, named ARI2m cells. Having demonstrated its efficacy, and in an at-tempt to avoid the immune rejection of CART cells by the patient, the single chain variable fragment was humanized, creating ARI2h cells. ARI2h cells demonstrated comparable in vitro and in vivo efficacy to ARI2m cells, and superiority in cases of high tumor burden disease. In terms of inflammatory response, ARI2h cells showed a lower TNFα production and lower in vivo toxicity profile. Large-scale expansion of both ARI2m and ARI2h cells was efficiently conducted following Good Manufacturing Practice guidelines, obtaining the target CART cell dose required for treatment of multiple myeloma patients. Moreover, we demonstrate that soluble BCMA and BCMA released in vesicles impacts on CAR-BCMA activity. In sum-mary, this study sets the bases for the implementation of a clinical trial (EudraCT code: 2019-001472-11) to study the efficacy of ARI2h cell treatment for multiple myeloma patients.
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Xiu Y, Dong Q, Fu L, Bossler A, Tang X, Boyce B, Borcherding N, Leidinger M, Sardina JL, Xue HH, Li Q, Feldman A, Aifantis I, Boccalatte F, Wang L, Jin M, Khoury J, Wang W, Hu S, Yuan Y, Wang E, Yuan J, Janz S, Colgan J, Habelhah H, Waldschmidt T, Müschen M, Bagg A, Darbro B, Zhao C

Coactivation of NF-κB and Notch signaling is sufficient to induce B-cell transformation and enables B-myeloid conversion.

Blood 9 Gen 2020, 135 (2) 108-120.
NF-κB and Notch signaling can be simultaneously activated in a variety of B-cell lymphomas. Patients with B-cell lymphoma occasionally develop clonally related myeloid tumors with poor prognosis. Whether concurrent activation of both pathways is sufficient to induce B-cell transformation and whether the signaling initiates B-myeloid conversion in a pathological context are largely unknown. Here, we provide genetic evidence that concurrent activation of NF-κB and Notch signaling in committed B cells is sufficient to induce B-cell lymphomatous transformation and primes common progenitor cells to convert to myeloid lineage through dedifferentiation, not transdifferentiation. Intriguingly, the converted myeloid cells can further transform, albeit at low frequency, into myeloid leukemia. Mechanistically, coactivation of NF-κB and Notch signaling endows committed B cells with the ability to self renew. Downregulation of BACH2, a lymphoma and myeloid gene suppressor, but not upregulation of CEBPα and/or downregulation of B-cell transcription factors, is an early event in both B-cell transformation and myeloid conversion. Interestingly, a DNA hypomethylating drug not only effectively eliminated the converted myeloid leukemia cells, but also restored the expression of green fluorescent protein, which had been lost in converted myeloid leukemia cells. Collectively, our results suggest that targeting NF-κB and Notch signaling will not only improve lymphoma treatment, but also prevent the lymphoma-to-myeloid tumor conversion. Importantly, DNA hypomethylating drugs might efficiently treat these converted myeloid neoplasms.
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