Publicació científica

S'han trobat 1304 publicacions amb els criteris indicats.
Beekman R, Chapaprieta V, Russiñol N, Vilarrasa-Blasi R, Verdaguer-Dot N, Martens JHA, Duran-Ferrer M, Kulis M, Serra F, Javierre BM, Wingett SW, Clot G, Queirós AC, Castellano G, Blanc J, Gut M, Merkel A, Heath S, Vlasova A, Ullrich S, Palumbo E, Enjuanes A, Martín-García D, Beà S, Pinyol M, Aymerich M, Royo R, Puiggros M, Torrents D, Datta A, Lowy E, Kostadima M, Roller M, Clarke L, Flicek P, Agirre X, Prosper F, Baumann T, Delgado J, López-Guillermo A, Fraser P, Yaspo ML, Guigó R, Siebert R, Martí-Renom MA, Puente XS, López-Otín C, Gut I, Stunnenberg HG, Campo E, Martin-Subero JI

The reference epigenome and regulatory chromatin landscape of chronic lymphocytic leukemia.

Nat. Med. Jun 2018, 24 (6) 868-880. Epub 21 Mai 2018
Chronic lymphocytic leukemia (CLL) is a frequent hematological neoplasm in which underlying epigenetic alterations are only partially understood. Here, we analyze the reference epigenome of seven primary CLLs and the regulatory chromatin landscape of 107 primary cases in the context of normal B cell differentiation. We identify that the CLL chromatin landscape is largely influenced by distinct dynamics during normal B cell maturation. Beyond this, we define extensive catalogues of regulatory elements de novo reprogrammed in CLL as a whole and in its major clinico-biological subtypes classified by IGHV somatic hypermutation levels. We uncover that IGHV-unmutated CLLs harbor more active and open chromatin than IGHV-mutated cases. Furthermore, we show that de novo active regions in CLL are enriched for NFAT, FOX and TCF/LEF transcription factor family binding sites. Although most genetic alterations are not associated with consistent epigenetic profiles, CLLs with MYD88 mutations and trisomy 12 show distinct chromatin configurations. Furthermore, we observe that non-coding mutations in IGHV-mutated CLLs are enriched in H3K27ac-associated regulatory elements outside accessible chromatin. Overall, this study provides an integrative portrait of the CLL epigenome, identifies extensive networks of altered regulatory elements and sheds light on the relationship between the genetic and epigenetic architecture of the disease.
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Martin R, Acha P, Ganster C, Palomo L, Dierks S, Fuster-Tormo F, Mallo M, Ademà V, Gómez-Marzo P, De Haro N, Solanes N, Zamora L, Xicoy B, Shirneshan K, Flach J, Braulke F, Schanz J, Kominowski A, Stromburg M, Brockmann A, Trümper L, Solé F, Haase D

Targeted deep sequencing of CD34+ cells from peripheral blood can reproduce bone marrow molecular profile in myelodysplastic syndromes.

Am. J. Hematol. Jun 2018, 93 (6) E152-E154. Epub 10 Abr 2018Més informació
Hurtado AM, Luengo-Gil G, Chen-Liang TH, Amaral F, Batta K, Palomo L, Lumbreras E, Przychodzen B, Caparros E, Amigo ML, Dıez-Campelo M, Zamora L, Salido Fierrez EJ, Maciejewski JP, Ortuño FJ, Vicente V, Del Canizo M, Sole F, Ferrer-Marin F, Wiseman DH, Jerez A

Transcriptomic rationale for synthetic lethality-targeting ERCC1 and CDKN1A in chronic myelomonocytic leukaemia.

Br. J. Haematol. 24 Mai 2018, . Epub 24 Mai 2018
Despite the absence of mutations in the DNA repair machinery in myeloid malignancies, the advent of high-throughput sequencing and discovery of splicing and epigenetics defects in chronic myelomonocytic leukaemia (CMML) prompted us to revisit a pathogenic role for genes involved in DNA damage response. We screened for misregulated DNA repair genes by enhanced RNA-sequencing on bone marrow from a discovery cohort of 27 CMML patients and 9 controls. We validated 4 differentially expressed candidates in CMML CD34
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García-Peydró M, Fuentes P, Mosquera M, García-León MJ, Alcain J, Rodríguez A, de Miguel PG, Menéndez P, Weijer K, Spits H, Scadden DT, Cuesta-Mateos C, Muñoz-Calleja C, Sánchez-Madrid F, Toribio ML

The NOTCH1/CD44 axis drives pathogenesis in a T cell acute lymphoblastic leukemia model.

J. Clin. Invest. 21 Mai 2018, . Epub 21 Mai 2018
NOTCH1 is a prevalent signaling pathway in T cell acute lymphoblastic leukemia (T-ALL), but crucial NOTCH1 downstream signals and target genes contributing to T-ALL pathogenesis cannot be retrospectively analyzed in patients and thus remain ill defined. This information is clinically relevant, as initiating lesions that lead to cell transformation and leukemia-initiating cell (LIC) activity are promising therapeutic targets against the major hurdle of T-ALL relapse. Here, we describe the generation in vivo of a human T cell leukemia that recapitulates T-ALL in patients, which arises de novo in immunodeficient mice reconstituted with human hematopoietic progenitors ectopically expressing active NOTCH1. This T-ALL model allowed us to identify CD44 as a direct NOTCH1 transcriptional target and to recognize CD44 overexpression as an early hallmark of preleukemic cells that engraft the BM and finally develop a clonal transplantable T-ALL that infiltrates lymphoid organs and brain. Notably, CD44 is shown to support crucial BM niche interactions necessary for LIC activity of human T-ALL xenografts and disease progression, highlighting the importance of the NOTCH1/CD44 axis in T-ALL pathogenesis. The observed therapeutic benefit of anti-CD44 antibody administration in xenotransplanted mice holds great promise for therapeutic purposes against T-ALL relapse.
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Sorigue M, Tuset V, Sancho JM

Treatment of localized-stage follicular lymphoma.

Eur. J. Haematol. 12 Mai 2018, . Epub 12 Mai 2018
Follicular lymphoma (FL) is the most common indolent lymphoma, and it most frequently presents in an advanced stage. Therapeutic considerations for advanced stage are different from those of localized-stage FL, in which radiotherapy (RT) is generally recommended. However, the available evidence suffers from shortcomings that are relatively specific to this clinical entity due to its rarity and long survival with all available treatment modalities, including that most of the existing evidence originated at a time when diagnostic classifications, staging procedures and radiotherapeutic standards were different from those available today and when anti-CD20 monoclonal antibodies were not available. Available treatment modalities include observation, systemic therapy only, RT only and RT in combination with systemic therapy. We review the evidence available with each of them and the data from present-day clinical practice studies as well as briefly discuss what diagnostic and therapeutic developments may take place in the next few years.
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Sorigue M, Sancho JM

Routine surveillance imaging in follicular lymphoma.

Ann. Hematol. 11 Mai 2018, . Epub 11 Mai 2018Més informació
Xicoy B, Triguero A, Such E, García O, Jiménez MJ, Arnán M, Bernal T, Diaz-Beya M, Valcárcel D, Pedro C, Ramos F, Amigo ML, Collado R, Palomo L, Ardanaz MT, Cedena MT, Grau J, Zamora L, Sanz G

The division of chronic myelomonocytic leukemia (CMML)-1 into CMML-0 and CMML-1 according to 2016 World Health Organization (WHO) classification has no impact in outcome in a large series of patients from the Spanish group of MDS.

Leuk. Res. 9 Mai 2018, 70 34-36. Epub 9 Mai 2018Més informació
Sorigue M, Gual-Capllonch F, Garcia O, Sarrate E, Franch-Sarto M, Ibarra G, Grau J, Orna E, Ribera JM, Sancho JM

Incidence, predictive factors, management, and survival impact of atrial fibrillation in non-Hodgkin lymphoma.

Ann. Hematol. 4 Mai 2018, . Epub 4 Mai 2018
Atrial fibrillation (AF) and cancer are common disorders in the general population but there are few studies in patients with both diseases. More specifically, there are scarce data on AF in patients with non-Hodgkin lymphoma (NHL). We assessed the incidence, predictive factors, management, and survival impact of AF in a cohort of patients with NHL from a single institution between 2002 and 2016 (n = 747). Twenty-three patients were diagnosed with AF before and 40 after the diagnosis of NHL (of the later, 16 were secondary to an extracardiac comorbidity and 24 unrelated to any triggering event [primary AF]). The 5-year cumulative incidence of new-onset AF was 4% (95% confidence interval [CI] 3-6%). Age and hypertension were the only predictive factors for the development of AF. Management of AF was heterogeneous, primarily with anti-vitamin K agents but also antiplatelet therapy in a significant proportion of patients. Among the 63 patients, there were six episodes of ischemic stroke/transient ischemic attack and four venous thromboembolic events, with four major bleeding episodes. Overall survival (OS) was inferior in patients with AF (HR 0.1, 95% CI 0.01-0.7, p = 0.02), largely due to secondary AF. We conclude that the incidence of new-onset AF in NHL patients seemed somewhat higher than in the general population, although with similar predictive factors. The management was heterogeneous, and the risk of ischemic and hemorrhagic events did not seem higher than in cancer-free patients. Survival was particularly poor for patients with secondary AF.
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Lu TT, Heyne S, Dror E, Casas E, Leonhardt L, Boenke T, Yang CH, Arrigoni L, Dalgaard K, Teperino R, Enders L, Selvaraj M, Ruf M, Raja SJ, Xie H, Boenisch U, Orkin SH, Lynn FC, Hoffman BG, Grün D, Vavouri T, Lempradl AM, Pospisilik JA

The Polycomb-Dependent Epigenome Controls β Cell Dysfunction, Dedifferentiation, and Diabetes.

Cell Metab. 4 Mai 2018, . Epub 4 Mai 2018
To date, it remains largely unclear to what extent chromatin machinery contributes to the susceptibility and progression of complex diseases. Here, we combine deep epigenome mapping with single-cell transcriptomics to mine for evidence of chromatin dysregulation in type 2 diabetes. We find two chromatin-state signatures that track β cell dysfunction in mice and humans: ectopic activation of bivalent Polycomb-silenced domains and loss of expression at an epigenomically unique class of lineage-defining genes. β cell-specific Polycomb (Eed/PRC2) loss of function in mice triggers diabetes-mimicking transcriptional signatures and highly penetrant, hyperglycemia-independent dedifferentiation, indicating that PRC2 dysregulation contributes to disease. The work provides novel resources for exploring β cell transcriptional regulation and identifies PRC2 as necessary for long-term maintenance of β cell identity. Importantly, the data suggest a two-hit (chromatin and hyperglycemia) model for loss of β cell identity in diabetes.
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Peña M, Serra J, Ribera JM

Cardiac arrest in a patient diagnosed with acute myeloid leukemia after the first dose of idarubicin.

Med Clin (Barc) 3 Mai 2018, . Epub 3 Mai 2018Més informació