A5064845209- Acute Myeloid Leukemia Research
- Histone Deacetylase Inhibitors Research
- Chronic Lymphocytic Leukemia Research
- Epigenetics and DNA Methylation
- Protein Degradation and Inhibitors
- Multiple Myeloma Research and Treatments
- CAR-T cell therapy research
- Lymphoma Diagnosis and Treatment
- Cancer-related gene regulation
- Immunodeficiency and Autoimmune Disorders
- FOXO transcription factor regulation
- COVID-19 and healthcare impacts
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- Genomics and Chromatin Dynamics
- Glycosylation and Glycoproteins Research
- CRISPR and Genetic Engineering
- Advances in Oncology and Radiotherapy
- Cell death mechanisms and regulation
- Blood disorders and treatments
- Single-cell and spatial transcriptomics
- 14-3-3 protein interactions
- Pancreatic function and diabetes
- IL-33, ST2, and ILC Pathways
- Immunotherapy and Immune Responses
Consorci Institut D'Investigacions Biomediques August Pi I Sunyer
2020-2025
Universitat de Barcelona
2023-2024
Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi i Sunyer
2023-2024
University of Manchester
2016-2023
Cancer Research UK Manchester Institute
2014-2023
Fundació Clínic per a la Recerca Biomèdica
2023
Spanish National Cancer Research Centre
2011-2017
Centre for Biomedical Network Research on Rare Diseases
2010-2011
Cancer Genetics (United States)
2011
Centro Nacional de Epidemiología
2009
Highlights•Inhibitors of LSD1 target both scaffolding and enzymatic functions the protein•GFI1/CoREST complex is targeted for disruption release from chromatin•GFI1/CoREST required leukemia cell differentiation•Loss enhancer-bound GFI1/LSD1 activates nearby myeloid differentiation genesSummaryPharmacologic inhibition promotes blast in acute (AML) with MLL translocations. The assumption has been that induced through blockade LSD1's histone demethylase activity. However, we observed rapid,...
Palatine tonsils are secondary lymphoid organs (SLOs) representing the first line of immunological defense against inhaled or ingested pathogens. We generated an atlas human tonsil composed >556,000 cells profiled across five different data modalities, including single-cell transcriptome, epigenome, proteome, and immune repertoire sequencing, as well spatial transcriptomics. This census identified 121 cell types states, defined developmental trajectories, enabled understanding functional...
CCS1477 (inobrodib) is a potent, selective EP300/CBP bromodomain inhibitor which induces cell-cycle arrest and differentiation in hematologic malignancy model systems. In myeloid leukemia cells, it promotes rapid eviction of from an enhancer subset marked by strong MYB occupancy high H3K27 acetylation, with downregulation the subordinate oncogenic network redistribution to sites close genes. myeloma FGFR3, target common (4; 14) translocation, away IRF4-occupied TCF3/E2A-occupied sites....
Background Aberrant promoter DNA methylation has been shown to play a role in acute myeloid leukemia (AML) pathophysiology. However, further studies discuss the prognostic value and relationship of epigenetic signatures with defined genomic rearrangements are required. Methodology/Principal Findings We carried out high-throughput profiling on 116 de novo AML cases we validated significant biomarkers an independent cohort 244 cases. Methylation were associated presence specific cytogenetic...
Inhibition of lysine specific demethylase 1 (LSD1) has been shown to induce the differentiation leukemia stem cells in acute myeloid (AML). Irreversible inhibitors developed from nonspecific inhibitor tranylcypromine have entered clinical trials; however, development effective reversible proved more challenging. Herein, we describe our efforts identify LSD1 a high throughput screen and subsequent silico modeling approaches. From single hit (12) validated by biochemical biophysical assays,...
Abstract Hotspot mutations in the PEST-domain of NOTCH1 and NOTCH2 are recurrently identified B cell malignancies. To address how NOTCH -mutations contribute to a dismal prognosis, we have generated isogenic primary human tumor cells from patients with Chronic Lymphocytic Leukemia (CLL) Mantle Cell Lymphoma (MCL), differing only their expression intracellular domain (ICD) or NOTCH2. Our data demonstrate that both NOTCH-paralogs facilitate immune-escape malignant by up-regulating PD-L1,...
unchanged over this period when adjusted for age, stage at diagnosis, time from diagnosis to transplant and disease status transplant.VRD has become the most common pretransplant induction regimen after 2010.Only, half of patients are placed on post-transplant treatment day 100 AHCT, with lenalidomide as frequently used agent.Counterintuitively, we did not see an increase in use maintenance recent period.Despite these impressive gains field, progression MM remains frequent cause death.
Abstract The histone demethylase lysine-specific 1 (LSD1 or KDM1A) has emerged as a candidate therapeutic target in acute myeloid leukaemia (AML); tranylcypromine-derivative inhibitors induce loss of clonogenic activity and promote differentiation, particular the MLL -translocated molecular subtype AML. In AML, use drugs combination often delivers superior clinical activity. To identify genes cellular pathways that collaborate with LSD1 to maintain leukaemic phenotype, which could be...
BTK inhibitor therapy induces peripheral blood lymphocytosis in chronic lymphocytic leukemia (CLL) lasting for several months. It remains unclear whether non-genetic adaptation mechanisms exist, allowing CLL cells' survival during inhibitor-induced and/or playing a role resistance. We show that approximately 70 % of cases, ibrutinib treatment vivo increases Akt activity above pre-therapy levels within weeks, leading to compensatory cell and more prominent on therapy. Ibrutinib-induced...
Pharmacologic inhibition of KDM1A (Lysine Demethylase 1A) induces differentiation in certain subtypes acute myeloid leukemia. Our recent studies reveal this is dependent upon drug-induced disruption the GFI1 (Growth Factor Independent 1) transcription repressor complex, leading to activation enhancers distributed close genes controlling monocytic lineage differentiation.
Chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) are 2 lymphoid neoplasms characterized by the proliferation accumulation of mature small CD5+ B cells, commonly involving bone marrow, blood, organs.1 CLL is considered an indolent disease, whereas clinical course majority MCL patients more aggressive. However, evolution both malignancies very heterogeneous. This heterogeneity exemplified major clinico-biological subtypes described in diseases, which level somatic...
The disruption of RUNX1 function is one the main mechanisms disease observed in hematopoietic malignancies and description novel genetic events that lead to a loss has been accelerated with development genomic technologies. Here we describe molecular characterization new t(4;21)(q21;q22) de novo myelodysplastic syndrome resulted deletion gene. We demonstrated by quantitative real-time RT-PCR an almost complete depletion expression gene our t(4;21) case compared CD34+ cells was independent...
Abstract Pharmacologic inhibition of LSD1 induces molecular and morphologic differentiation blast cells in acute myeloid leukemia (AML) patients harboring MLL gene translocations. In addition to its demethylase activity, has a critical scaffolding function at genomic sites occupied by the SNAG domain transcription repressor GFI1. Importantly, inhibitors block both enzymatic activities, latter case disrupting protein:protein interaction GFI1 with LSD1. To explore wider consequences on protein...