A5026475228- Acute Lymphoblastic Leukemia research
- Acute Myeloid Leukemia Research
- DNA and Nucleic Acid Chemistry
- Cancer Genomics and Diagnostics
- Genomics and Phylogenetic Studies
- Epigenetics and DNA Methylation
- Chronic Myeloid Leukemia Treatments
- Environmental DNA in Biodiversity Studies
- Identification and Quantification in Food
- Cancer-related gene regulation
- Single-cell and spatial transcriptomics
- PI3K/AKT/mTOR signaling in cancer
- Genetically Modified Organisms Research
- Lymphoma Diagnosis and Treatment
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Chronic Lymphocytic Leukemia Research
- Monoclonal and Polyclonal Antibodies Research
- RNA modifications and cancer
- Genomic variations and chromosomal abnormalities
- Animal Genetics and Reproduction
- Microbial Community Ecology and Physiology
- Histone Deacetylase Inhibitors Research
- Biochemical and Molecular Research
- Pluripotent Stem Cells Research
Princess Máxima Center
2019-2025
Oncode Institute
2022-2025
Wageningen University & Research
2017-2019
DNA metabarcoding provides great potential for species identification in complex samples such as food supplements and traditional medicines. Such a method would aid Convention on International Trade Endangered Species of Wild Fauna Flora (CITES) enforcement officers to combat wildlife crime by preventing illegal trade endangered plant animal species. The objective this research was develop multi-locus forensic evaluate the applicability reproducibility approach across different laboratories....
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 Protein kinase inhibitors are amongst the most successful cancer treatments, but targetable kinases activated by genomic abnormalities rare in T cell acute lymphoblastic leukemia. Nevertheless, can be absence of genetic defects. Thus, phosphoproteomics provide information on pathway activation and signaling networks that offer opportunities for targeted therapy. Here, we describe a mass spectrometry-based global phosphoproteomic profiling 11 leukemia lines to identify kinases. We...
• MinION DNA metabarcoding is a promising tool for species identification in food. and Illumina MiSeq sequencing platforms perform equally accurate. Species with requires dedicated bioinformatics.
Background: The Notch signal transduction pathway is pivotal for various physiological processes, including immune responses, and has been implicated in the pathogenesis of many diseases. effectiveness targeted inhibitors may vary due to variabilities activity among individual patients. quantitative measurement therefore essential identify patients who could benefit from treatment. Methods: We here describe a new assay that infers score mRNA levels generally conserved direct NOTCH target...
Current intensive chemotherapy regimens have improved overall survival in pediatric acute lymphoblastic leukemia (ALL) but fail to cure some high-risk patient subgroups. We observed that lysine methyltransferase 2A (KMT2A)-rearranged leukemia, an aggressive subset with a dismal prognosis, is particularly vulnerable perturbations of the methionine cycle. demonstrate this dependency driven by increased need for S-adenosylmethionine (SAM) maintain hypermethylated state KMT2A-r leukemias....
Long-range oncogenic enhancers play an important role in cancer. Yet, whether similar regulation of tumor suppressor genes is relevant remains unclear. Loss expression PTEN associated with the pathogenesis various cancers, including T-cell leukemia (T-ALL). Here, we identify a highly conserved distal enhancer (PE) that interacts promoter multiple hematopoietic populations, T-cells, and acts as hub transcription factors T-ALL. Consistently, loss PE leads to reduced levels T-ALL cells....
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...
Abstract In KMT2A -rearranged acute lymphoblastic leukemia (ALL), an aggressive malignancy, oncogenic KMT2A-fusion proteins inappropriately recruit DOT1L to promote leukemogenesis, highlighting as attractive therapeutic target. Unfortunately, treatment with the first-in-class inhibitor pinometostat eventually leads non-responsiveness. To understand this we established acquired resistance in pediatric KMT2A::AFF1 + B-ALL cells. Interestingly, these cells became mostly independent of...
Abstract Leukemia is characterized by oncogenic lesions that result in a block of differentiation, whereas phenotypic plasticity retained. A better understanding how these two phenomena arise during leukemogenesis humans could help inform diagnosis and treatment strategies. Here, we leveraged the well-defined differentiation states T-cell development to pinpoint initiation acute lymphoblastic leukemia (T-ALL), an aggressive form childhood leukemia, study emergence plasticity. Single-cell...
The majority of feed products in industrialised countries contains materials derived from genetically modified organisms (GMOs). In parallel, the number reports unauthorised GMOs (UGMOs) is gradually increasing. There a lack specific detection methods for UGMOs, due to absence detailed sequence information and reference materials. this research, an adapted genome walking approach was developed, called ALF: Amplification Linearly-enriched Fragments. Coupling ALF NGS aims simultaneous...
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...
Constitutional mismatch repair deficiency (CMMRD) is a high-risk childhood cancer predisposition syndrome caused by biallelic germline mutations in one of the four (MMR) genes MLH1, MSH2, MSH6, or PMS2. Defective MMR results rapid accumulation and continuous development malignancies from an early age. The tumor spectrum CMMRD patients consists mostly high-grade brain tumors, gastrointestinal (GI) hematologic malignancies.1 Hematologic are predominantly lymphomas, most which T-cell...
In pediatric Acute Lymphoblastic Leukemia (ALL), mutations/deletions affecting the TP53 gene are rare at diagnosis. However, relapse about 12% of patients show aberrations, predicting a very poor outcome. Since p53-mediated apoptosis is an endpoint for many cytotoxic drugs, loss p53 function frequently leads to therapy failure. this study, we that CRISPR/Cas9-induced drives resistance large majority drugs used treat relapsed ALL, including novel agents such as inotuzumab ozogamicin. Using...
<p>Supplementary Figures</p>
<div>Abstract<p>Leukemia is characterized by oncogenic lesions that result in a block of differentiation, whereas phenotypic plasticity retained. A better understanding how these two phenomena arise during leukemogenesis humans could help inform diagnosis and treatment strategies. Here, we leveraged the well-defined differentiation states T-cell development to pinpoint initiation acute lymphoblastic leukemia (T-ALL), an aggressive form childhood leukemia, study emergence...