A5032046854- Acute Myeloid Leukemia Research
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Genomics and Chromatin Dynamics
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Blood disorders and treatments
- Chronic Lymphocytic Leukemia Research
- Immune Response and Inflammation
- RNA Interference and Gene Delivery
- Renal and related cancers
- Gastrointestinal Tumor Research and Treatment
- Glycosylation and Glycoproteins Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cancer Genomics and Diagnostics
- Immune cells in cancer
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Metastasis and carcinoma case studies
- Single-cell and spatial transcriptomics
- Hematopoietic Stem Cell Transplantation
- Neuroblastoma Research and Treatments
- Cell Adhesion Molecules Research
- Advanced biosensing and bioanalysis techniques
- Cytokine Signaling Pathways and Interactions
- Cancer-related gene regulation
Weizmann Institute of Science
2021-2023
Erasmus MC
2011-2021
Oncode Institute
2021
Erasmus University Rotterdam
2012-2015
University of Toronto
2015
Structural Genomics Consortium
2015
We performed cytosine methylation sequencing on genetically diverse patients with acute myeloid leukemia (AML) and found leukemic DNA patterning is primarily driven by nonpromoter regulatory elements CpG shores. Enhancers displayed stronger differential than promoters, consisting predominantly of hypomethylation. AMLs dominant hypermethylation featured greater epigenetic disruption whereas those hypomethylation distal intronic regions. Mutations in IDH DNMT3A had opposing mutually exclusive...
C/EBPs are a family of transcription factors that regulate growth control and differentiation various tissues. We found C/EBPγ is highly upregulated in subset acute myeloid leukemia (AML) samples characterized by C/EBPα hypermethylation/silencing. Similarly, was murine hematopoietic stem/progenitor cells lacking C/EBPα, as mediates suppression. Studies demonstrated CEBPG overexpression blocked neutrophilic differentiation. Further, downregulation Cebpg Cebpa-deficient or human CEBPA-silenced...
Acute myeloid leukemia (AML) is associated with mutations in transcriptional and epigenetic regulator genes impairing differentiation. The t(8;21)(q22;q22) translocation generates the RUNX1-ETO fusion protein, which interferes hematopoietic master RUNX1. We previously showed that maintenance of t(8;21) AML dependent on expression. Its depletion causes extensive changes transcription factor binding, as well gene expression, initiates However, how these processes are connected within a...
The transcription factor C/EBPa initiates the neutrophil gene expression program in bone marrow (BM). Knockouts of Cebpa or its +37kb enhancer mice show 2 major findings: (1) neutropenia BM and blood; (2) decrease long-term hematopoietic stem cell (LT-HSC) numbers. Whether latter finding is cell-autonomous (intrinsic) to LT-HSCs an extrinsic event exerted on compartment remained open question. Flow cytometric analysis knockout model revealed that reduction LT-HSC numbers observed was...
<p>DMC identity and annotation for all clusters. This is part 3/3 (file split by columns due to upload limitations)</p>
<p>The supplementary methods contain a more detailed description of the analytic and experimental approach beyond scope main section. Supplementary Figure S1. Ability specific genomic lesions to predict epigenetic clustering. S2. ERRBS coverage. S3. Differential methylation at promoters active enhancers. S4. DMC distribution. S5. Transcription factor binding site analysis differentially methylated enhancers in IDH2, DNMT3A, IDH1/DNMT3A AMLs.</p>
<p>DMC identity and annotation for IDH2, DNMT3A, IDH1/DNMT3A cohorts.</p>
<p>DMC identity and annotation for mouse Idh2, Dnmt3a, Idh2/Dnmt3a cohorts.</p>
<p>Detailed information including ERRBS cluster identity, HELP cytogenetics, molecular profile, and limited profile of mutations genetic perturbations.</p>
<p>Extended high throughput mutation profiling.</p>
<p>DMC identity and annotation for all clusters. This is part 2/3 (file split by columns due to upload limitations)</p>
<p>DMC identity and annotation for all clusters. This is part 1/3 (file split by columns due to upload limitations)</p>
<p>DMC identity and annotation for all clusters. This is part 3/3 (file split by columns due to upload limitations)</p>