Expression data changes induced by 3D conditions in T-ALL cells [CCRF-CEM cells]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE190771 | GEO | 2023/12/13
REPOSITORIES: GEO
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Project description:3D constrained conditions promoted H3K4 methylation in ALL cells that altered the global chromatin configuration and transcriptional changes related to cell cycle and DNA replication.
2024-08-05 | GSE181375 | GEO
Project description:3D constrained conditions promoted H3K4 methylation in ALL cells that altered the global chromatin configuration and transcriptional changes related to cell cycle and DNA replication.
2023-07-27 | GSE216698 | GEO
Project description:Expression data changes induced by 3D conditions in T-ALL cells [CCRF-CEM cells]
| PRJNA788450 | ENA
Project description:Glucocorticoids play an essential part in anti-leukemic therapies, but resistance is a crucial event for the prognosis of the disease. Glucocorticoids influence the metabolic properties of leukemic cells. The inherent plasticity of clinically evolving cancer cells justifies the characterization of drug-induced early oncogenic pathways, which represent a likely source of detrimental secondary effects. The present work aims to investigate the effect of glucocorticoids in metabolic pathways in the CCRF-CEM leukemic cells. Metabolic factors and gene expression profiles were examined in order to unravel the possible mechanisms of the CCRF-CEM leukemic cell growth dynamics. CCRF-CEM cells were used as a model. Cells were treated with prednisolone with concentrations 0-700 μM. Cell culture supernatants were used for glucose, lactic acid, LDH, Na+, K+ and Ca++ measurements. Cytotoxicity was determined with flow cytometry. Microarray analysis was performed using two different chips of 1.2 k and 4.8 k genes. Gene Ontology enrichment analysis was applied to find metabolism- and GC-related genes. Higher prednisolone concentrations inhibited glucose uptake, without exhibiting any cytotoxic effects. Glucose consumption did not correlate with the total cell population, or the viable population, indicating that growth is not directly proportional to glucose consumption. Neither of the subpopulations, i.e., viable, necrotic, or apoptotic cells, contributed to this. Different types of leukemic cells seem to exhibit different patterns of glucose metabolism. Both resistant and sensitive CCRF-CEM cells followed the aerobic pathway of glycolysis. There is probably a rapid change in membrane permeability, causing a general shutdown towards everything that is outside the cell. This could in part also explain the observed resistance. Glucocorticoids do not enter the cell passively anymore and therefore no effects are observed. Based on our observations, ion concentrations are measurable factors both in vitro and in vivo, which makes them possible markers of glucocorticoid cytotoxic action.
| S-EPMC8198442 | biostudies-literature
Project description:Purpose: Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer and infiltration of leukemic cells is critical for disease progression and relapse. In spite of the canonical functions of epigenetics in transcription and DNA homeostasis, its contribution to the nuclear deformability of migrating leukemic cells remains unclear. The objective was to evaluate the role of WDR5 (a core subunit of the histone H3K4 methyltransferases) during leukemia cell migration. Experimental design: We used ALL cell lines and primary samples from patients to study their response and migration in 3D environments and how they extravasate in a mouse xenograft model. We also performed, biophysical, transcriptional and ChIP-sequencing analyses to determine the mechanism by which WDR5 controls ALL progression. Results: We observed that WDR5 activity is critical for ALL cell invasion into 3D collagen matrices. Notably, blocking WDR5 activity also decreased the extravasation of ALL cells in an in vivo model. We identified that 3D constrained conditions promoted H3K4 methylation in ALL cells that altered the global chromatin configuration and transcriptional changes related to cell cycle and DNA replication. WDR5 inhibition did not impair cell adhesion or cell response to chemokines; but we demonstrated that 3D conditions affected the deformation and biophysical behavior of the nucleus in ALL cells. Conclusions: We conclude that confined conditions have a fundamental role in ALL cell biology and provide novel molecular and biophysical mechanisms used by leukemia cells to disseminate. Targeting WDR5 might be a promising therapeutic strategy against ALL infiltration and dissemination.
2024-01-14 | GSE193383 | GEO
Project description:Purpose: Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer and infiltration of leukemic cells is critical for disease progression and relapse. In spite of the canonical functions of epigenetics in transcription and DNA homeostasis, its contribution to the nuclear deformability of migrating leukemic cells remains unclear. The objective was to evaluate the role of WDR5 (a core subunit of the histone H3K4 methyltransferases) during leukemia cell migration. Experimental design: We used ALL cell lines and primary samples from patients to study their response and migration in 3D environments and how they extravasate in a mouse xenograft model. We also performed, biophysical, transcriptional and ChIP-sequencing analyses to determine the mechanism by which WDR5 controls ALL progression. Results: We observed that WDR5 activity is critical for ALL cell invasion into 3D collagen matrices. Notably, blocking WDR5 activity also decreased the extravasation of ALL cells in an in vivo model. We identified that 3D constrained conditions promoted H3K4 methylation in ALL cells that altered the global chromatin configuration and transcriptional changes related to cell cycle and DNA replication. WDR5 inhibition did not impair cell adhesion or cell response to chemokines; but we demonstrated that 3D conditions affected the deformation and biophysical behavior of the nucleus in ALL cells. Conclusions: We conclude that confined conditions have a fundamental role in ALL cell biology and provide novel molecular and biophysical mechanisms used by leukemia cells to disseminate. Targeting WDR5 might be a promising therapeutic strategy against ALL infiltration and dissemination.
2024-01-11 | GSE193440 | GEO
Project description:Resistance to asparaginase, an antileukemic enzyme that depletes asparagine, is a common clinical problem. Using a genome-wide CRISPR/Cas9 screen, we found a synthetic lethal interaction between Wnt pathway activation and asparaginase in acute leukemias resistant to this enzyme. Wnt pathway activation induced asparaginase sensitivity in distinct treatment-resistant subtypes of acute leukemia, but not in normal hematopoietic progenitors. Sensitization to asparaginase was mediated by Wnt-dependent stabilization of proteins (Wnt/STOP), which inhibits GSK3-dependent protein ubiquitination and proteasomal degradation, a catabolic source of asparagine. Inhibiting the alpha isoform of GSK3 phenocopied this effect, and pharmacologic GSK3 inhibition profoundly sensitized drug-resistant leukemias to asparaginase. Our findings provide a molecular rationale for activation of Wnt/STOP signaling to improve the therapeutic index of asparaginase. To gain further insights into mechanisms of cytotoxicity of this combination, we applied unbiased mass spectrometry proteomics to CCRF-CEM cells, a human T-cell acute lymphoblastic leukemia cell line, treated with vehicle, asparaginase alone, the GSK3 inhibitor BRD0705 (which phenocopies Wnt/STOP pathway activation), or the combination of asparaginase and BRD0705.
2019-03-29 | PXD013061 | Pride
Project description:Acute lymphoblastic leukemia (ALL) accounts for approximately 75% of childhood leukemia, and chemotherapy remains the mainstay therapy. Baicalein is an active flavonoid used in traditional Chinese medicine and has recently been found to have anticancer, anti-inflammatory, and antiallergic properties. This study aims to investigate the molecular apoptotic mechanisms of baicalein in CCRF-CEM leukemic cells and to evaluate the combined therapeutic efficacy of baicalein with several commonly used chemotherapeutic drugs in CCRF-CEM cells. Our results demonstrate that baicalein induces mitochondria-dependent cleavage of caspases-9 and -3 and PARP with concomitant decreases in IAP family proteins, survivin, and XIAP. Furthermore, our results present for the first time that baicalein triggers a convergence of the intrinsic and extrinsic apoptotic pathways via the death receptor-caspase 8-tBid signaling cascade in CCRF-CEM cells. In addition, we also present for the first time that the combination of baicalein and vincristine results in a synergistic therapeutic efficacy. Overall, this combination strategy is recommended for future clinical trials in the treatment of pediatric leukemia owing to baicalein's beneficial effects in alleviating the vomiting, nausea, and skin rashes caused by chemotherapy.
| S-EPMC3580913 | biostudies-literature
Project description:The present study was undertaken to identify proteins that interact with the mammalian target of rapamycin complex 1 (mTORC1) to enable it to carry out its crucial cell signaling functions. Endogenous and myc-tag mTORC1 was purified, in-gel tryptic digested and then identified by nano-LC ESI Q-TOF MS/MS analysis. A total of nine novel interacting proteins were identified in both endogenous and myc-tag mTORC1 purifications. These new mTORC1 interacting partners include heterogeneous nuclear ribonucleoproteins A2/B1, enhancer of mRNA decapping protein 4, 60S acidic ribosomal protein, P0, nucleolin, dynamin 2, glyceraldehyde 3 phosphate dehydrogenase, 2-oxoglutarate dehydrogenase, glycosyl transferase 25 family member 1 and prohibitin 2. Furthermore hnRNP A2/B1 and dynamin 2 interaction with mTORC1 was confirmed on immunoblotting. The present study has for the first time identified novel interacting partners of mTORC1 in human T lymphoblasts (CCRF-CEM) and human embryonic kidney (HEK293) cells. These new interacting proteins may offer new targets for therapeutic interventions in human diseases caused by perturbed mTORC1 signaling.
| S-EPMC3975426 | biostudies-literature
Project description:Background: Glucocorticoids are important pharmaceutical agents in the treatment of acute lymphoblastic leukemia in children. Resistance or sensitivity to glucocorticoids is considered to be of crucial importance for disease prognosis. Prednisolone is a first-line chemotherapeutic agent in the treatment of acute lymphoblastic leukemia. Here, the effects of prednisolone on the resistant CCRF-CEM leukemic cell line were studied. Methods: Prednisolone’s cytotoxic and cell cycle effects were studied with flow cytometry. NF-κB translocation was studied with Western Blotting and differential gene expression was studied with cDNA microarrays. Results: Prednisolone exerted a delayed biphasic effect, necrotic at low doses and apoptotic at higher doses. At low doses, prednisolone exerted a pre-dominant mitogenic effect despite its induction on total cell death, while at higher doses, prednisolone’s mitogenic and cell death effects were counterbalanced. NF-κB was constitutively present in the nucleus. Early gene microarray analysis revealed 40 differentially expressed genes upon 4 hours of prednisolone’s exposure. Notable differences in gene regulation were observed between the lowest and the highest glucocorticoid doses. Prednisolone activated genes related to apoptosis/tumor suppression, cell cycle progression, metabolism and intra-/ extra-cellular signaling pathways. Conclusions: The mitogenic/biphasic effects of prednisolone are of clinical importance in the case of resistant leukemic cells. This approach might lead to the identification of gene candidates for future molecular drug targets in combination therapy with glucocorticoids, along with early markers for glucocorticoid resistance.
2011-03-22 | GSE27989 | GEO