5b589469-9d3c-4cd7-9cba-ad614d7313b4 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001009501 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Count matrix from 44 pre-treatment (Ven-Obi or Clb-Obi) and 44 paired, post-treatment relapsed CD19+ B cells.
| EGAD00001009500 | EGA
Project description:RNAseq FASTq files from 418 pre-treatment (Ven-Obi or Clb-Obi) CD19+ B cells.
| EGAD00001009418 | EGA
Project description:RNAseq FASTq files from 44 pre-treatment (Ven-Obi or Clb-Obi) and 44 paired,
post-treatment relapsed CD19+ B cells.
| EGAD00001009419 | EGA
Project description:CLL14 (NCT02242942) is a multinational, open-label Phase III study designed to compare venetoclax-obinutuzumab (Ven-Obi) versus chlorambucil-obinutuzumab (Clb-Obi) in previously untreated patients with CLL and co-existing conditions. Between Aug 7, 2015, and Aug 4, 2016, 432 patients were enrolled and randomly assigned to receive either venetoclax plus obinutuzumab (Ven-Obi, n=216) or chlorambucil plus obinutuzumab (Clb-Obi, n=216). In both study arms, patients received fixed-duration treatment of overall 12 cycles, each cycle 28 days long, and entered subsequent post-treatment surveillance. Peripheral blood samples were collected before the start of therapy, as well as every 3-6 months during and after therapy, including at the time of disease progression. The primary endpoint of the study was progression-free survival, secondary endpoints included overall response rate, minimal residual disease response, and overall survival. The primary read-out was conducted after a median follow-up of 28.1 months, when the primary endpoint was met with 30 primary end-point events (disease progression or death) in the Ven-Obi arm and 77 in the Clb-Obi arm (hazard ratio, 0.35; 95% confidence interval [CI], 0.23 to 0.53;P<0.001). Follow-up is ongoing until 9 years after the last patient enrollment. In an exploratory analysis, bulk RNAseq was conducted with CD19-enriched blood from patients before start of therapy (418 patients) and at first relapse (44 patients).
| EGAS00001006596 | EGA
Project description:RNA-seq count matrix for 296 bulk pre-treatment tumors from IMblaze370
| EGAD00001008552 | EGA
Project description:To elucidate the underlying mechanisms of resistance to venetoclax and dexitabine combination therapy, we performed transcriptomic analysis of VEN/DEC pre- and post-treatment samples from AML patients enrolled in the DEC10-VEN clinical trial (NCT03404193). We have reported that AML cells from non-responders show a significant upregulation of the mRNA expression of the fatty acid metabolism activator PPARG (Peroxisome Proliferator-Activated Receptor γ) after VEN/DEC treatment.
2025-08-06 | GSE270621 | GEO
Project description:Purpose: To show that 8-Cl-Ado can target FAO and synergizes with VEN to significantly decrease the oxygen consumption rate (OCR) and in turn OXPHOS in CD34-enriched AML cells. Methods: Using AML cell lines and LSC-enriched blast cells from pre-treatment AML patients, we evaluated the effects of 8-Cl-Ado, VEN and the 8-Cl-Ado/VEN combination on fatty acid metabolism, glycolysis and OXPHOS using liquid scintillation counting, a Seahorse XF Analyzer and gene set enrichment analysis (GSEA). Results: We here report that VEN and 8-Cl-Ado synergistically inhibited in vitro growth of AML cells. Furthermore, immunodeficient mice engrafted with MV4-11-Luc AML cells and treated with the combination of VEN plus 8-Cl-Ado had a significantly longer survival than mice treated with either drugs alone (p≤0.006). Conclusion: Taken together, the results suggest that 8-Cl-Ado enhances the antileukemic activity of VEN and that this combination represents a promising therapeutic regimen for treatment of AML.
2021-04-07 | GSE171552 | GEO
Project description:Background: The combination of hypomethylating agents (HMA) with the Bcl-2 inhibitor venetoclax (VEN) has significantly advanced acute myeloid leukemia (AML) treatment. This therapy is approved for older patients and those with comorbidities. Objectives: We aimed to identify resistance mechanisms to HMA-VEN therapy using scRNA-Seq on primary AML samples. GLUT5 expression on AML progenitors from resistant and non-resistant patients was evaluated through immunoblotting and immunofluorescence. Seahorse and CRISPR experiments were conducted to validate the phenotype in the THP-1 AML monocyte cell line. Findings: scRNA-Seq revealed an upregulation of Leukemia Stem Cell (LSC) 17 scores in pre-treatment samples compared to HMA-VEN relapse samples. RNA velocity analysis indicated that LSCs in pre-treatment samples were the root cell population, while HMA-VEN relapse cells, specifically AML Blast 1, showed preferential splicing of PHGDH, a key serine synthesis pathway member, resulting in the overexpression of SLC2A5. GLUT5 was more frequently and intensely expressed on the cell surface in patients resistant to HMA-VEN. Seahorse assays demonstrated that fructose uptake via GLUT5 suppressed oxygen consumption in THP-1 cells following siRNA-mediated knockdown. Conclusions: Aberrant GLUT5 expression by leukemia progenitors represents a metabolic adaptation contributing to VEN resistance in AML.
2025-09-20 | GSE277678 | GEO
Project description:Venetoclax (ven) combined with the hypomethylating agent azacytidine (aza) is a widely used therapy for Acute Myeloid Leukemia (AML), however, most patients develop resistance. A genome-wide CRISPR screen showed that loss of genes involved in translation conferred sensitivity to ven but not ven+palbo. Accordingly, we show that increased translation occurs after AML cells are challenged with ven, and ven+palbo blocks this increase. We also found that loss of BAX, which leads to ven resistance, was overcome by combination with CDK4/6 inhibitors. Conversely, loss of RB1, a known mechanism of resistance to CDK4/6 inhibitors, was mitigated by ven+palbo. This work suggests that the combination of ven+palbo is a potential novel therapy for AML for potential subpopulations that may benefit the most from this treatment, as well as targeting translation as a means to overcome ven resistance.
2025-11-11 | GSE291338 | GEO
Project description:Deep single-cell multi-omic profiling of drug resistance in patients with relapsed or refractory (rr) acute myeloid leukemia (AML) is a promising approach to understand and identify the molecular and cellular determinants of drug resistance. Here, we address this challenge by integrating single-cell ex vivo drug profiling (pharmacoscopy) with both bulk and single-cell resolved DNA, RNA, and protein profiling, as well as clinical annotations across samples of a cohort of 21 rrAML patients. Unsupervised data integration revealed ex vivo response to the Bcl-2 inhibitor venetoclax (VEN) to be significantly reduced in patients treated with the combination of a hypomethylating agent (HMA) and VEN compared to patients pre-exposed to HMA only, while also exposing innate Ven resistance in a subset of VEN-naive patients. Systematic molecular integration retrieved known and novel molecular mechanisms underlying VEN resistance and identified alternative therapeutic strategies in VEN resistant samples, including targeting increased proliferation by PLK inhibitor volasertib. Across data modalities, high CD36 expression on AML blasts was associated with VENres, while CD36-targeted antibody treatment ex vivo revealed striking sensitivity in VEN resistant AML. In summary, we showcase how single-cell multi-omic and functional profiling can facilitate the discovery of drug resistance mechanisms and emergent treatment vulnerabilities. Our dataset represents a comprehensive molecular and functional profiling of rrAML at single-cell resolution, providing a valuable resource for future studies.
| MSV000092970 | MassIVE