A5060220645- Acute Myeloid Leukemia Research
- Granular flow and fluidized beds
- Cytokine Signaling Pathways and Interactions
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cyclone Separators and Fluid Dynamics
- Fluid Dynamics and Mixing
- Hematopoietic Stem Cell Transplantation
- Particle Dynamics in Fluid Flows
- Cancer, Hypoxia, and Metabolism
- Immune cells in cancer
- Epigenetics and DNA Methylation
- Chronic Myeloid Leukemia Treatments
- Minerals Flotation and Separation Techniques
- Metabolomics and Mass Spectrometry Studies
- Chronic Lymphocytic Leukemia Research
- Cancer Genomics and Diagnostics
- Fluid Dynamics and Heat Transfer
- Eosinophilic Disorders and Syndromes
- Histone Deacetylase Inhibitors Research
- Mineral Processing and Grinding
- Cancer, Lipids, and Metabolism
- Skin and Cellular Biology Research
- Tryptophan and brain disorders
- Analog and Mixed-Signal Circuit Design
- Otitis Media and Relapsing Polychondritis
The University of Adelaide
1990-2024
South Australian Health and Medical Research Institute
2021-2024
Kaohsiung Medical University
2017-2024
Kaohsiung Medical University Chung-Ho Memorial Hospital
2017-2024
UNSW Sydney
1988-2006
National University of Singapore
2004
University of British Columbia
1995-1999
Abstract Isocitrate dehydrogenase 1 and 2 (IDH) are mutated in multiple cancers drive production of (R)-2-hydroxyglutarate (2HG). We identified a lipid synthesis enzyme [acetyl CoA carboxylase (ACC1)] as synthetic lethal target mutant IDH1 (mIDH1), but not mIDH2, cancers. Here, we analyzed the metabolome primary acute myeloid leukemia (AML) blasts an mIDH1-specific reduction fatty acids. mIDH1 also induced switch to b-oxidation indicating reprogramming metabolism toward reliance on Compared...
Report14 February 2022Open Access Source DataTransparent process Targeting human CALR-mutated MPN progenitors with a neoepitope-directed monoclonal antibody Denis Tvorogov orcid.org/0000-0002-2009-1347 Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, Australia Contribution: Conceptualization, Formal analysis, Supervision, Funding acquisition, Validation, Investigation, Visualization, Methodology, Writing - original draft, review & editing Search more...
Abstract Rare preleukemic hematopoietic stem cells (pHSC) harboring only the initiating mutations can be detected at time of acute myeloid leukemia (AML) diagnosis. pHSCs are origin and a potential reservoir for relapse. Using primary human samples gene editing to model isocitrate dehydrogenase 1 (IDH1) mutant pHSCs, we show epigenetic, transcriptional, metabolic differences between healthy (HSC). We confirm that IDH1-driven clonal hematopoiesis is associated with cytopenia, suggesting an...
High prevalence of IDH mutations in seronegative rheumatoid arthritis (RA) with myeloid neoplasm, elevated 2-hydroxyglutarate, dysregulated innate immunity, and proinflammatory microenvironment suggests causative association between RA. Our findings merit investigation inhibitors as therapeutics for IDH-mutated
Abstract The interaction of germline variation and somatic cancer driver mutations is under-investigated. Here we describe the genomic mitochondrial landscape in adult acute myeloid leukaemia (AML) show that rare variants affecting nuclear- mitochondrially-encoded complex I genes near-mutual exclusivity with isocitrate dehydrogenase 1 ( IDH1 ), but not IDH2 suggesting a unique epistatic relationship. Whereas AML cells or all display attenuated respiration, heightened sensitivity to...
Therapy-related myeloid neoplasm (tMN) is considered a direct consequence of DNA damage in hematopoietic stem cells. Despite increasing recognition that altered stroma can also drive leukemogenesis, the functional biology tMN microenvironment remains unknown. We performed multiomic (transcriptome, response, cytokine secretome and profiling) characterization bone marrow stromal cells from patients. Critically, we compared (i) patients with another cancer but without cytotoxic exposure, (ii)...
Abstract Lateral and axial profiles of solids cross‐flow flux were measured in a circulating fluidized bed riser square cross‐section with sampling probe. The was found to be higher near the wall, especially corners, lower core riser. net horizontal outwards part inwards top. lateral momentum flux, by means piezoelectric probe, increased height then decreased top first distance from axis towards wall. It low corners.
In vivo and in vitro studies have demonstrated that thrombospondin-1 (TSP-1) is involved atherosclerotic pathogenesis. However, the role of TSP-1 clinical atherosclerosis remains unknown. This cross-sectional study investigated relationship between carotid intima–media thickness (IMT) examined whether it interacts with conventional cardiovascular risk factors. A total 587 participants were enrolled from February 2018 to December 2021. was dichotomized based on median value. Carotid IMT...
<div>Abstract<p>Rare preleukemic hematopoietic stem cells (pHSC) harboring only the initiating mutations can be detected at time of acute myeloid leukemia (AML) diagnosis. pHSCs are origin and a potential reservoir for relapse. Using primary human samples gene editing to model <i>isocitrate dehydrogenase 1</i> (<i>IDH1</i>) mutant pHSCs, we show epigenetic, transcriptional, metabolic differences between healthy (HSC). We confirm that...
<p>Supplementary Figure 1. IDH2 is mutated in preleukemic hematopoietic stem cells relapse causing clones AML. Supplementary 2. Single-cell RNA sequencing and combined genotyping reveal distinct transcriptomic profiles of IDH1-mutant pHSCs AML 3. Modeling human using CRISPR/Cas9 with HDR show reduced proliferation blocked differentiation caused by IDH1 mutations 4. reduce 5-hydroxymethylcytosine gene bodies 5. drives alterations 6. are sensitive to inhibition oxidative phosphorylation</p>
<p>Supplementary Figure 1. IDH2 is mutated in preleukemic hematopoietic stem cells relapse causing clones AML. Supplementary 2. Single-cell RNA sequencing and combined genotyping reveal distinct transcriptomic profiles of IDH1-mutant pHSCs AML 3. Modeling human using CRISPR/Cas9 with HDR show reduced proliferation blocked differentiation caused by IDH1 mutations 4. reduce 5-hydroxymethylcytosine gene bodies 5. drives alterations 6. are sensitive to inhibition oxidative phosphorylation</p>
<div>Abstract<p>Rare preleukemic hematopoietic stem cells (pHSC) harboring only the initiating mutations can be detected at time of acute myeloid leukemia (AML) diagnosis. pHSCs are origin and a potential reservoir for relapse. Using primary human samples gene editing to model <i>isocitrate dehydrogenase 1</i> (<i>IDH1</i>) mutant pHSCs, we show epigenetic, transcriptional, metabolic differences between healthy (HSC). We confirm that...
Chronic myelomonocytic leukemia (CMML) is a rare blood cancer of older adults (3 in every 1,000,000 persons) characterized by poor survival and lacking effective mutation-specific therapy. Mutations the ubiquitin ligase Cbl occur frequently CMML share biological molecular features with clonal disease occurring children, juvenile (JMML). Here we analyzed clinical presentations, immunophenotype patients CBL mutations enrolled prospective Phase II trial stratified according to markers....