Similar Datasets
Project description:Rosetta (Merck) Expression Validated Gene Hybridizations
| PRJNA87935 | ENA
Project description:Acute myeloid leukemia (AML) is the most common and severe acute leukemia in adults. It is a heterogeneous disease where the subset of molecularly different types, presenting various morphological features and differentiation stage, can be distinguished. Genomic research of leukemias is conducted since 1999 and large cohort studies shown that particular genetic alterations correspond with specific gene expression signatures. However, not always they provide clinically relevant information. The most unknown group is cytogenetically normal acute myeloid leukemia (CN-AML, 40-49% of all AML cases). The aim of our experiment was to determine selected gene expression profiles in CN-AML, using small, boutique microarray. The array contained 933 oligonucleotide probes, mainly complementary to acute myeloid leukemia markers, genes involved in leukemic transformation and myeloid cell proliferation, differentiation and maturation. Our test dataset included 40 hybridizations: 24 corresponding with blood and bone marrow samples collected from 12 patients with AML M1 or M2 FAB subtype and 16 corresponding with healthy control samples. Total RNA was extracted from the mononuclear cell fractions, reversibly transcribed to cDNA and labeled with Alexa 647 dye. The common reference was RNA isolated from HL-60 cell culture, labeled with Alexa 555 dye.
2013-07-01 | E-MEXP-3647 | biostudies-arrayexpress
Project description:Acute myeloid leukemia (AML) is a hematologic malignancy with a poor prognosis. We discovered that BMAL1 is a ferroptosis suppressor. Furthermore, it was also found to be overexpressed in AML patients, affecting the cell cycle and promoting tumor cell growth and progression. In this study, we further validated the association of BMAL1 with the progression and survival outcomes of AML. Lipidomic revealed that the levels of ceramide increased in AML cells following the depletion of BMAL1. Ceramide facilitated ferroptosis in AML cells. ASAH2 played a key role in this process. BMAL1 could not directly regulate ASAH2 but instead through IKZF2. Elevated levels of ceramide promoted the degradation of the ferroptosis protection molecule GPX4, ultimately promoting ferroptosis. Furthermore, ceramide treatment has been demonstrated to enhance the responsiveness of AML cells to sorafenib. In summary, this study elucidates that BMAL1 depletion remodels ceramide metabolism to regulate the sensitivity of AML cells to ferroptosis and targeted drug sorafenib.
2025-01-24 | MTBLS11557 | MetaboLights
Project description:The paper describes a model of acute myeloid leukaemia.
Created by COPASI 4.26 (Build 213)
This model is described in the article:
Optimal control of acute myeloid leukaemia
Jesse A. Sharp, Alexander P Browning, Tarunendu Mapder, Kevin Burrage, Matthew J Simpson
Journal of Theoretical Biology 470 (2019) 30–42
Abstract:
Acute myeloid leukaemia (AML) is a blood cancer affecting haematopoietic stem cells. AML is routinely treated with chemotherapy, and so it is of great interest to develop optimal chemotherapy treatment strategies. In this work, we incorporate an immune response into a stem cell model of AML, since we find that previous models lacking an immune response are inappropriate for deriving optimal control strategies. Using optimal control theory, we produce continuous controls and bang-bang controls, corre- sponding to a range of objectives and parameter choices. Through example calculations, we provide a practical approach to applying optimal control using Pontryagin’s Maximum Principle. In particular, we describe and explore factors that have a profound influence on numerical convergence. We find that the convergence behaviour is sensitive to the method of control updating, the nature of the control, and to the relative weighting of terms in the objective function. All codes we use to implement optimal control are made available.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models .
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2024-09-02 | BIOMD0000000798 | BioModels
Project description:Comparison of cross-species and species-specific hybridizations
| PRJNA93673 | ENA
Project description:<p>Acute myeloid leukemia (AML) is an aggressive disease with a high relapse rate. In this study, we map the metabolic profile of CD34+(CD38low/-) AML cells and the extracellular vesicle signatures in circulation from AML patients at diagnosis. CD34+ AML cells display high antioxidant glutathione levels and enhanced mitochondrial functionality, both associated with poor clinical outcomes. Although CD34+ AML cells are highly dependent on glucose oxidation and glycolysis for energy, those from intermediate- and adverse-risk patients reveal increased mitochondrial dependence. Extracellular vesicles from AML are mainly enriched in stem cell markers and express antioxidant GPX3, with their profiles showing potential prognostic value. Extracellular vesicles enhance mitochondrial functionality and dependence on CD34+ AML cells via the glutathione/GPX4 axis. Notably, only extracellular vesicles from adverse-risk patients enhance leukemia cell engraftment in vivo. Here, we show a potential noninvasive approach based on liquid ‘cell-extracellular vesicle’ biopsy toward a redefined metabolic stratification in AML.</p><p><br></p><p><strong>Lipidomic analysis on extracellular vesicles</strong> is reported in the current study <a href='https://www.ebi.ac.uk/metabolights/MTBLS11523' rel='noopener noreferrer' target='_blank'><strong>MTBLS11523</strong></a>.</p><p><strong>Metabolomic analysis on extracellular vesicles</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS11746' rel='noopener noreferrer' target='_blank'><strong>MTBLS11746</strong></a>.</p>
2024-12-04 | MTBLS11523 | MetaboLights
Project description:<p>Acute myeloid leukemia (AML) is an aggressive disease with a high relapse rate. In this study, we map the metabolic profile of CD34+(CD38low/-) AML cells and the extracellular vesicle signatures in circulation from AML patients at diagnosis. CD34+ AML cells display high antioxidant glutathione levels and enhanced mitochondrial functionality, both associated with poor clinical outcomes. Although CD34+ AML cells are highly dependent on glucose oxidation and glycolysis for energy, those from intermediate- and adverse-risk patients reveal increased mitochondrial dependence. Extracellular vesicles from AML are mainly enriched in stem cell markers and express antioxidant GPX3, with their profiles showing potential prognostic value. Extracellular vesicles enhance mitochondrial functionality and dependence on CD34+ AML cells via the glutathione/GPX4 axis. Notably, only extracellular vesicles from adverse-risk patients enhance leukemia cell engraftment in vivo. Here, we show a potential noninvasive approach based on liquid ‘cell-extracellular vesicle’ biopsy toward a redefined metabolic stratification in AML.</p><p><br></p><p><strong>Metabolomic analysis on extracellular vesicles</strong> is reported in the current study <a href='https://www.ebi.ac.uk/metabolights/MTBLS11746' rel='noopener noreferrer' target='_blank'><strong>MTBLS11746</strong></a>.</p><p><strong>Lipidomic analysis on extracellular vesicles</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS11523' rel='noopener noreferrer' target='_blank'><strong>MTBLS11523</strong></a>.</p>
2024-12-04 | MTBLS11746 | MetaboLights
Project description:Despite early optimism, therapeutics targeting oxidative phosphorylation (OxPhos) have faced clinical setbacks, primarily stemming from their inability to distinguish healthy from cancerous mitochondria. Herein, we describe an actionable bioenergetic mechanism unique to cancerous mitochondria inside acute myeloid leukemia (AML) cells. Unlike healthy cells which couple respiration to the synthesis of ATP, AML mitochondria were discovered to support inner membrane polarization by consuming ATP. Because matrix ATP consumption allows cells to survive bioenergetic stress, we hypothesized that AML cells may resist cell death induced by OxPhos damaging chemotherapy by reversing the ATP synthase reaction. In support of our hypothesis, targeted inhibition of BCL-2 with venetoclax abolished OxPhos flux without impacting mitochondrial membrane potential. In surviving AML cells, sustained polarization of the mitochondrial inner membrane was dependent on matrix ATP consumption. Mitochondrial ATP consumption was further enhanced in AML cells made refractory venetoclax, consequential to downregulations in both the proton-pumping respiratory complexes, as well the endogenous F1-ATPase inhibitor ATP5IF1. In treatment-naive AML, ATP5IF1 knockdown was sufficient to drive venetoclax resistance, while ATP5IF1 overexpression impaired F1-ATPase activity and heightened sensitivity to venetoclax. Collectively, our data identify matrix ATP consumption as cancer-cell intrinsic bioenergetic vulnerability actionable in the context of mitochondrial damaging chemotherapy.
2025-04-02 | PXD051129 | JPOST Repository