A5050284841- Acute Lymphoblastic Leukemia research
- T-cell and Retrovirus Studies
- Immune Cell Function and Interaction
- Chronic Myeloid Leukemia Treatments
- Acute Myeloid Leukemia Research
- RNA Interference and Gene Delivery
- Epigenetics and DNA Methylation
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- Inflammatory Bowel Disease
- Genomics and Chromatin Dynamics
- CAR-T cell therapy research
- Lymphoma Diagnosis and Treatment
- RNA modifications and cancer
- Protein purification and stability
- 14-3-3 protein interactions
- Cancer Genomics and Diagnostics
- Cancer-related gene regulation
- Patient Dignity and Privacy
- Palliative Care and End-of-Life Issues
- Inflammation biomarkers and pathways
- Cell death mechanisms and regulation
- Adenosine and Purinergic Signaling
- Viral gastroenteritis research and epidemiology
- Galectins and Cancer Biology
Erasmus MC
2010-2025
Princess Máxima Center
2016-2024
Erasmus MC - Sophia Children’s Hospital
2010-2016
PI3K/AKT pathway mutations are found in T-cell acute lymphoblastic leukemia, but their overall impact and associations with other genetic aberrations is unknown. PTEN have been proposed as secondary that follow NOTCH1-activating cause cellular resistance to γ-secretase inhibitors.The of PTEN, PI3K AKT was studied a genetically well-characterized pediatric leukemia patient cohort (n=146) treated on DCOG or COALL protocols.PTEN E17K were detected 13% 2% patients, respectively. Defective...
Pediatric acute lymphoblastic leukemia (ALL) is the most common childhood cancer and leading cause of cancer-related mortality in children. T cell ALL (T-ALL) represents about 15% pediatric cases considered a high-risk disease. T-ALL often associated with resistance to treatment, including steroids, which are currently cornerstone for treating ALL; moreover, initial steroid response strongly predicts survival cure. However, cellular mechanisms underlying patients poorly understood. In this...
We identified mutations in the IL7Ra gene or genes encoding downstream signaling molecules JAK1, JAK3, STAT5B, N-RAS, K-RAS, NF1, AKT and PTEN 49% of patients with pediatric T-cell acute lymphoblastic leukemia (T-ALL). Strikingly, these (except RAS/NF1) were mutually exclusive, suggesting that they each cause aberrant activation a common target. Expressing mutant molecules-but not their wild-type counterparts-rendered Ba/F3 cells independent IL3 by activating RAS-MEK-ERK PI3K-AKT pathways....
Three distinct immature T-cell acute lymphoblastic leukemia entities have been described including cases that express an early precursor immunophenotype or expression profile, MEF2C-dysregulated cluster based on gene analysis (immature cluster) and retain non-rearranged TRG@ loci. Early exclusively overlap with samples the of signature genes, indicating both are featuring a single disease entity. Patients lacking rearrangements represent only 40% cases, but no further evidence was found to...
Contemporary biomedical research increasingly depends on techniques to induce or inhibit expression of genes in hematopoietic stem cells (HSCs) other primary assess their roles cellular processes including differentiation, apoptosis and migration. Surprisingly little information is available optimize lentiviral transduction HSCs. We have therefore carefully optimized murine human HSCs by optimizing vector design, serum-free virus production quantitation. conclude that the viral RNA length,...
Rearrangements that drive ectopic MEF2C expression have recurrently been found in patients with human early thymocyte progenitor acute lymphoblastic leukemia (ETP-ALL). Here, we show high levels of ETP-ALL. Using both vivo and vitro models ETP-ALL, demonstrate elevated blocks NOTCH-induced T cell differentiation while promoting a B-lineage program. activates B transcriptional program addition to RUNX1, GATA3, LMO2; upregulates the IL-7R; boosts survival by upregulation BCL2. Notch pathway,...
Abstract Background Neutrophils are key players in intestinal damage Crohn’s disease (CD) and ulcerative colitis (UC) but their immunological role heterogeneity is largely overlooked. In both diseases, mature circulating neutrophils enter the tissue to clear invading bacteria cause irreversible damage. However, neutrophil function can be altered by pathogenic Th1/17 CD4+ memory T cell (Tm) responses even before cells tissue. We hypothesize that differs between, within, CD UC interpatient...
Deletion of chromosome 6q is a well-recognized abnormality found in poor-prognosis T-cell acute lymphoblastic leukemia (T-ALL). Using integrated genomic approaches, we identified two candidate haploinsufficient genes contiguous at 6q14, SYNCRIP (encoding hnRNP-Q) and SNHG5 (that hosts snoRNAs), both involved regulating RNA maturation translation. Combined silencing genes, but not either gene alone, accelerated leukemogeneis Tal1/Lmo1/Notch1-driven mouse model, demonstrating the...
Monoallelic inactivation of CCCTC-binding factor (CTCF) in human cancer drives altered methylated genomic states, CTCF occupancy at promoter and enhancer regions, deregulated global gene expression. In patients with T cell acute lymphoblastic leukemia (T-ALL), we find that acquired monoallelic CTCF-inactivating events drive subtle local effects nearly half t(5; 14) (q35; q32.2) rearranged patients, especially when CTCF-binding sites are preserved between the BCL11B TLX3 oncogene. These...
The glucocorticoid receptor NR3C1 is essential for steroid-induced apoptosis, and deletions of this gene have been recurrently identified at disease relapse acute lymphoblastic leukemia (ALL) patients. Here, we demonstrate that recurrent inactivating aberrations—including deletions, missense, nonsense mutations—are in 7% pediatric T-cell ALL patients diagnosis. These aberrations are frequently present early thymic progenitor-ALL relate to steroid resistance. Functional modeling pre-B cell...
Physiological and pathogenic interleukin-7-receptor (IL7R)-induced signaling provokes glucocorticoid resistance in a subset of patients with pediatric T-cell acute lymphoblastic leukemia (T-ALL). Activation downstream STAT5 has been suggested to cause steroid through upregulation anti-apoptotic BCL2, one its target genes. Here we demonstrate that isolated various T-ALL cell models is insufficient raise cellular despite BCL2 BCL-XL. Upregulation BCLXL STAT5-activated cells requires...
Abstract Background Neutrophils clear luminal bacteria from the intestinal lamina propria and have a protective role in Inflammatory Bowel Disease (IBD). However, their production of inflammatory cytokines, matrix metalloproteases radical oxygen species causes irreversible tissue damage. Histological assessment infiltrating neutrophils indirect measurement neutrophil-derived calprotectin feces are used to assess disease severity patients. Since IBD is heterogeneous terms presentation,...
The dissociation and association behaviour of 70-S ribosomes Escherichia coli has been studied. It shown that the dissociation-association reaction can be both a real dynamic equilibrium non-equilibrium reaction, dependent upon ionic conditions solvent. At relatively high strength (I = 0.15 M or more) is an whereas at lower 0.1 less) there no between its subunits. In latter case hysteresis in observed. Whether not demonstrated by single centrifugation experiment, using analytical ultracentrifuge.
Abstract Background Inflammatory bowel disease, comprising Crohn’s disease (CD) and ulcerative colitis (UC), is driven by aberrant host-microbial immune interactions. Disease heterogeneity severity hamper effective treatment, thus new therapeutic strategies tailored to the patient’s underlying defect are required. In mice, upon epithelial barrier breach microbiota inflammation, colonic intestinal cells increase Secretory Leukocyte Protease Inhibitor (SLPI) expression. SLPI can exert...
<div>Abstract<p>Deletion of chromosome 6q is a well-recognized abnormality found in poor-prognosis T-cell acute lymphoblastic leukemia (T-ALL). Using integrated genomic approaches, we identified two candidate haploinsufficient genes contiguous at 6q14, <i>SYNCRIP</i> (encoding hnRNP-Q) and <i>SNHG5</i> (that hosts snoRNAs), both involved regulating RNA maturation translation. Combined silencing genes, but not either gene alone, accelerated leukemogeneis...
<p>Supp Fig. S1-6, Supp Tables S1-S3, Methods and References</p>
<div>Abstract<p>Deletion of chromosome 6q is a well-recognized abnormality found in poor-prognosis T-cell acute lymphoblastic leukemia (T-ALL). Using integrated genomic approaches, we identified two candidate haploinsufficient genes contiguous at 6q14, <i>SYNCRIP</i> (encoding hnRNP-Q) and <i>SNHG5</i> (that hosts snoRNAs), both involved regulating RNA maturation translation. Combined silencing genes, but not either gene alone, accelerated leukemogeneis...
<p>Differentially Expressed Proteins Deleted versus non-deleted clones</p>