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Mohty M.,University Pierre and Marie Curie | Malard F.,University Pierre and Marie Curie | Abecassis M.,Institute Portugues Oncologia | Aerts E.,University of Zurich | And 26 more authors.
Bone Marrow Transplantation

Sinusoidal obstruction syndrome or veno-occlusive disease (SOS/VOD) is a potentially life-threatening complication of hematopoietic SCT (HSCT). This review aims to highlight, on behalf of the European Society for Blood and Marrow Transplantation, the current knowledge on SOS/VOD pathophysiology, risk factors, diagnosis and treatments. Our perspectives on SOS/VOD are (i) to accurately identify its risk factors; (ii) to define new criteria for its diagnosis; (III) to search for SOS/VOD biomarkers and (iv) to propose prospective studies evaluating SOS/VOD prevention and treatment in adults and children. © 2015 Macmillan Publishers Limited. Source

Navarro A.,University of Barcelona | Munoz C.,University of Barcelona | Gaya A.,Hospital Clinic | Diaz-Beya M.,Hospital Clinic | And 6 more authors.

Background:In recent years, microRNA (miRNA) pathways have emerged as a crucial system for the regulation of tumorogenesis. miR-SNPs are a novel class of single nucleotide polymorphisms that can affect miRNA pathways.Design and Methods:We analyzed eight miR-SNPs by allelic discrimination in 141 patients with Hodgkin lymphoma and correlated the results with treatment-related toxicity, response, disease-free survival (DFS) and overall survival (OS).Results:The KRT81 (rs3660) GG genotype was associated with an increased risk of neurological toxicity (P = 0.016), while patients with XPO5 (rs11077) AA or CC genotypes had a higher rate of bleomycin-associated pulmonary toxicity (P = 0.048). Both miR-SNPs emerged as independent factors in the multivariate analysis. The XPO5 AA and CC genotypes were also associated with a lower response rate (P = 0.036). XPO5 (P = 0.039) and TRBP (rs784567) (P = 0.022) genotypes emerged as prognostic markers for DFS, and XPO5 was also associated with OS (P = 0.033). In the multivariate analysis, only XPO5 emerged as an independent prognostic factor for DFS (HR: 2.622; 95%CI 1.039-6.620; P = 0.041). Given the influence of XPO5 and TRBP as individual markers, we then investigated the combined effect of these miR-SNPs. Patients with both the XPO5 AA/CC and TRBP TT/TC genotypes had the shortest DFS (P = 0.008) and OS (P = 0.008).Conclusion:miR-SNPs can add useful prognostic information on treatment-related toxicity and clinical outcome in Hodgkin lymphoma and can be used to identify patients likely to be chemoresistant or to relapse. © 2013 Navarro et al. Source

Carreras E.,Hospital Clinic | Carreras E.,Josep Carreras Leukaemia Research Institute
British Journal of Haematology

Summary: Sinusoidal obstruction syndrome (SOS), also called veno-occlusive disease of the liver, is one of the most relevant complications of endothelial origin that appears early after haematopoietic cell transplantation (HCT). Despite its relatively low incidence and the fact that most cases of SOS resolve spontaneously, the cases that evolve to multi-organ failure (MOF; severe SOS) have a mortality rate higher than 80% and represent one of the major clinical problems after HCT. For this reason, transplantation teams must have a pre-established policy regarding preventive measures in high-risk patients, strict daily control of weight and fluid balance during HCT, homogeneous diagnostic criteria, appropriate complementary studies for a correct differential diagnosis and measures to prevent and manage hepatorenal syndrome; in addition they must also be ready to start early treatment with defibrotide in patients with a possible severe SOS. Due to the lack of definitive evidence to enable the establishment of general recommendations in the management of SOS, this review analyses all of these aspects based on the author's personal experience. © 2014 John Wiley & Sons Ltd. Source

Miguel-Escalada I.,Imperial College London | Miguel-Escalada I.,Institute dInvestigacions August Pi I Sunyer IDIBAPS | Miguel-Escalada I.,CIBER ISCIII | Pasquali L.,CIBER ISCIII | And 5 more authors.
Current Opinion in Genetics and Development

In recent years, studies of cis-regulatory mechanisms have evolved from a predominant focus on promoter regions to the realization that spatial and temporal gene regulation is frequently driven by long-range enhancer clusters that operate within chromosomal compartments. This increased understanding of genome function, together with the emergence of technologies that enable whole-genome sequencing of patients' DNAs, open the prospect of dissecting the role of cis-regulatory defects in human disease. In this review we discuss how recent epigenomic studies have provided insights into the function of transcriptional enhancers. We then present examples that illustrate how integrative genomics can help uncover enhancer sequence variants underlying Mendelian and common polygenic human disease. © 2015 The Authors. Source

Cebola I.,Imperial College London | Pasquali L.,Germans Trias i Pujol University Hospital and Research Institute | Pasquali L.,Josep Carreras Leukaemia Research Institute | Pasquali L.,CIBER ISCIII
Journal of Molecular Endocrinology

Most of the genetic variation associated with diabetes, through genome-wide association studies, does not reside in protein-coding regions, making the identification of functional variants and their eventual translation to the clinic challenging. In recent years, highthroughput sequencing-based methods have enabled genome-scale high-resolution epigenomic profiling in a variety of human tissues, allowing the exploration of the human genome outside of the well-studied coding regions. These experiments unmasked tens of thousands of regulatory elements across several cell types, including diabetes-relevant tissues, providing new insights into their mechanisms of gene regulation. Regulatory landscapes are highly dynamic and cell-type specific and, being sensitive to DNA sequence variation, can vary with individual genomes. The scientific community is now in place to exploit the regulatory maps of tissues central to diabetes etiology, such as pancreatic progenitors and adult islets. This giant leap forward in the understanding of pancreatic gene regulation is revolutionizing our capacity to discriminate between functional and nonfunctional non-coding variants, opening opportunities to uncover regulatory links between sequence variation and diabetes susceptibility. In this review, we focus on the non-coding regulatory landscape of the pancreatic endocrine cells and provide an overview of the recent developments in this field. © 2016 Society for Endocrinology. Source

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