A5075553324- Acute Myeloid Leukemia Research
- Immune cells in cancer
- Hematopoietic Stem Cell Transplantation
- Extracellular vesicles in disease
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Blood disorders and treatments
- Animal testing and alternatives
- Immunodeficiency and Autoimmune Disorders
- Single-cell and spatial transcriptomics
- MicroRNA in disease regulation
- Infrared Thermography in Medicine
- RNA Interference and Gene Delivery
- Mesenchymal stem cell research
- Epigenetics and DNA Methylation
- Acute Lymphoblastic Leukemia research
- Cell Adhesion Molecules Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Drug Transport and Resistance Mechanisms
- Molecular Biology Techniques and Applications
- Immune Cell Function and Interaction
- Erythrocyte Function and Pathophysiology
- Neutropenia and Cancer Infections
- Hematological disorders and diagnostics
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
Erasmus MC
2011-2025
Erasmus MC Cancer Institute
2016-2025
Erasmus University Rotterdam
2016-2022
Cancer Institute (WIA)
2022
Harvard University
2008-2010
Massachusetts General Hospital
2008-2010
Harvard Stem Cell Institute
2008
Radboud University Nijmegen
2002-2007
Radboud University Medical Center
2002-2007
Radboud Institute for Molecular Life Sciences
2007
Production of the cells that ultimately populate thymus to generate α/β T has been controversial, and their molecular drivers remain undefined. Here, we report specific deletion bone-producing osteocalcin (Ocn)-expressing in vivo markedly reduces T-competent progenitors thymus-homing receptor expression among bone marrow hematopoietic cells. Decreased intrathymic cell precursors decreased generation mature occurred despite normal thymic function. The Notch ligand DLL4 is abundantly expressed...
Peptide receptor radionuclide therapy (PRRT) may induce long-term toxicity to the bone marrow (BM). The aim of this study was analyze persistent hematologic dysfunction (PHD) after PRRT with <sup>177</sup>Lu-DOTATATE in patients gastroenteropancreatic neuroendocrine tumors (GEP NETs). <b>Methods:</b> incidence and course PHD were analyzed 274 GEP NET from a group 367 somatostatin receptor–positive tumors. defined as diagnosis myelodysplastic syndrome (MDS), acute myeloid leukemia (AML),...
Vexas syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a recently identified, treatment-refractory, inflammatory developing in late adulthood with fevers, cytopenias, characteristic vacuoles myeloid and erythroid precursor cells, dysplastic bone marrow, neutrophilic cutaneous pulmonary inflammation, chondritis, vasculitis, an often fatal outcome.1,2 Effective treatments have not yet been established. Here, we report genetic, morphologic, clinical remissions 2 of 3 VEXAS...
Abstract The bone marrow microenvironment influences malignant hematopoiesis, but how it promotes leukemogenesis has not been elucidated. In addition, the role of stroma in regulating clinical responses to DNA methyltransferase inhibitors (DNMTi) is also poorly understood. this study, we conducted a methylome analysis marrow–derived stromal cells from myelodysplastic syndrome (MDS) patients and observed widespread aberrant cytosine hypermethylation occurring preferentially outside CpG...
Abstract Cancer initiation is orchestrated by an interplay between tumor-initiating cells and their stromal/immune environment. Here, adapted single-cell RNA sequencing, we decipher the predicted signaling tissue-resident hematopoietic stem/progenitor (HSPC) neoplastic counterparts with native niches in human bone marrow. LEPR+ stromal are identified as central regulators of hematopoiesis through interactions all Inflammatory niche remodeling resulting deprivation critical HSPC regulatory...
VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is an inflammatory syndrome caused by acquired mutations in the gene encoding ubiquitin like modifier activating enzyme 1 (UBA1) that often fatal.1, 2 Allogeneic hematopoietic stem cell transplantation currently considered only curative treatment modality.3-6 We were first to report eradication of virtually all UBA1-mutated cells hypomethylating agent azacitidine, reflected clinical and genetic remissions,7 a finding confirmed...
Abstract Purpose: Acute myeloid leukemia (AML) is considered a stem cell disease. Incomplete chemotherapeutic eradication of leukemic CD34+38− cells likely to result in disease relapse. The purpose this study was investigate the role breast cancer resistance protein (BCRP/ATP-binding cassette, subfamily G, member 2) drug and effect its modulation on AML. Experimental Design: BCRP expression (measured flow-cytometrically using BXP21 monoclonal antibody) (using novel fumitremorgin C analogue...
Shwachman-Diamond syndrome is a congenital bone marrow failure disorder characterized by debilitating neutropenia. The disease associated with loss-of-function mutations in the SBDS gene, implicated ribosome biogenesis, but cellular and molecular events driving cell specific phenotypes ribosomopathies remain poorly defined. Here, we established what to our knowledge first mammalian model of neutropenia through targeted downregulation Sbds hematopoietic stem progenitor cells expressing...
Hairy cell leukemia (HCL) is a chronic, incurable B malignancy that presents with splenomegaly, bone marrow infiltration, and cytopenias [1].Long remissions are typically achieved purine analogs such as cladribine, but most cases will relapse require further therapy.The discovery of the
Abstract During embryogenesis, lymph nodes form through intimate interaction between lymphoid tissue inducer and organizer (LTo) cells. Shortly after birth in mice, specialized stromal cell subsets arise that organize microenvironments within the nodes; however, their direct precursors have not yet been identified. In bone marrow, mesenchymal stem cells are labeled with GFP nestin-GFP we show during all stages of development, nestin+ present these mice. At day birth, both CD31− endothelial...
Abstract Osteolineage cells represent one of the critical bone marrow niche components that support maintenance hematopoietic stem and progenitor (HSPCs). Recent studies demonstrate extracellular vesicles (EVs) regulate cell development via horizontal transfer bioactive cargo, including microRNAs (miRNAs). Using next-generation sequencing we show human osteoblast-derived EVs contain highly abundant miRNAs specifically enriched in EVs, regulators proliferation (e.g., miR-29a). EV treatment...
Bone marrow (BM) mesenchymal stromal cells (MSCs) provide microenvironmental support to hematopoietic stem and progenitor (HSPCs). Culture-expanded MSCs are interesting candidates for cellular therapies due their immunosuppressive regenerative potential which can be further enhanced by pretreatment with interferon-gamma (IFN-γ). However, it remains unknown whether IFN-γ also influence BM-MSCs. In this study, we elucidate the impact of on We found that increases expression interleukin (IL)-6...