Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Determinants of venetoclax resistance

ABSTRACT: Determinants of venetoclax resistance

PROVIDER: PRJNA558092 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Determinants of venetoclax resistance

Project description:Determinants of venetoclax resistance

| PRJNA558091 | ENA

Genetic determinants of venetoclax resistance

Project description:Genetic determinants of venetoclax resistance

| PRJNA528105 | ENA

Genetic determinants of venetoclax resistance

Project description:Resistance to the first approved BCL-2 inhibitor venetoclax is emerging in lymphoid malignancies. The study aimed to identify the genetic determinants of such resistance. From genome-scale screens we determined the genes influencing the sensitivity to BCL-2 inhibition. The present set of data is related to expression changes (assessed by RNA sequencing) observed in the resistant OCI-Ly1 lymphoma cell line as well as those resulting from genetic perturbation (using CRISPR-Cas9) targeting the genes highlighted in our genome-scale screen.

2019-09-25 | GSE128563 | GEO

Assessing DNA methylation differences upon aquired Venetoclax resistance

Project description:We analyzed DNA methylation alterations upon acquired Venetoclax resistance using 8 different cell line pairs

2023-11-22 | GSE166577 | GEO

Venetoclax resistance leads to broad resistance to standard-of-care anti-MM agents, but not to immunotherapies

Project description:Venetoclax is the first example of personalized medicine for multiple myeloma (MM), with meaningful clinical activity as a monotherapy and in combination in myeloma patients harboring the t(11:14) translocation. However, despite the high response rates and prolonged PFS, a significant proportion of patients eventually relapse. Here, we aimed to study adaptive molecular responses after the acquisition of venetoclax resistance in sensitive t(11:14) MM cell models. We therefore generated single-cell venetoclax-resistant t(11:14) MM cell lines and investigated the mechanisms contributing to resistance as well as the cells’ sensitivity to other treatments. Our data suggests that acquired resistance to venetoclax is characterized by reduced mitochondrial priming and changes in BCL-2 family proteins’ expression in MM cells, conferring broad resistance to standard-of-care anti-myeloma drugs. However, our results show that the resistant cells are still sensitive to immunotherapeutic treatments, highlighting the need to consider appropriate sequencing of these treatments following venetoclax-based regimens.

2024-06-06 | GSE269245 | GEO

BRD4 and MYB Inhibition Overcomes Venetoclax Resistance in EVI1-rearranged Acute Myeloid Leukemia

Project description:EVI1-rearranged acute myeloid leukemia (AML) with inv(3)(q21q26) or t(3;3)(q21q26) represents a distinct and aggressive subtype characterized by poor prognosis and limited treatment options. However, the optimal strategy to overcome resistance to conventional therapy remains elusive. Building upon observations correlating EVI1 overexpression with reduced sensitivity to venetoclax, a BH3-mimetic inhibitor, we investigated the mechanisms of resistance to venetoclax in combination with hypomethylating agents in inv(3)/t(3;3) AML cells. Utilizing novel murine models recapitulating inv(3) AML with concomitant SF3B1 mutations, we conducted comprehensive phenotypic and transcriptomic analyses in the presence or absence of venetoclax-containing therapy. Despite initial therapeutic responses, manifested as partially prolonged survival and myeloid differentiation, resistant leukemic cells demonstrated enhanced dependency on BRD4 and MYB pathways with a dormant phenotype. Notably, inhibition of either BRD4 or MYB significantly augmented the efficacy of venetoclax and hypomethylating agents in both murine and patient-derived AML models harboring inv(3) and SF3B1 mutations. These findings elucidate the transcriptional dynamics underlying venetoclax resistance and propose alternative therapeutic strategies targeting BRD4 and MYB as promising avenues for improving outcomes in patients with EVI1-rearranged AML. Our work highlights the necessity for innovative combination therapies to address the multifaceted mechanisms of resistance in this high-risk leukemia subtype.

2025-12-02 | GSE292744 | GEO

AKT inhibitor capivasertib reverses EVI1‑driven resistance to venetoclax in acute myeloid leukaemia

Project description:Acute myeloid leukaemia (AML) with MECOM rearrangement is recognized by the World Health Organization as a distinct entity characterized by poor prognosis and aggressive disease progression. We demonstrated that elevated EVI1 expression confers resistance to venetoclax by stabilizing MCL‑1 through activation of the PI3K/AKT signalling pathway in vitro. Mechanistically, elevated EVI1 levels were associated with increased phosphorylation of MCL-1 at threonine 163 (T163pMCL‑1), thereby stabilizing MCL-1 by attenuating its ubiquitin–proteasome mediated degradation. Importantly, cotreatment with venetoclax and the clinically available AKT inhibitor capivasertib effectively restored sensitivity in both cell lines and patient-derived primary AML samples with high EVI1 expression. Overall, our findings reveal a novel molecular mechanism underlying EVI1-mediated venetoclax resistance through PI3K/AKT-driven MCL‑1 stabilization and suggest a combination strategy involving AKT inhibition as a promising approach for overcoming therapeutic resistance in this high-risk AML subset.

2026-04-08 | GSE326738 | GEO

Assessing DNA methylation differences upon aquired Venetoclax resistance

Project description:Assessing DNA methylation differences upon aquired Venetoclax resistance

| PRJNA701295 | ENA

Effect of venetoclax, tedizolid, and combination treatment on gene expression in a venetoclax-resistant AML cell line

Project description:The goal of this study was to profile the changes in gene expression in an AML cell line with acquired resistance to venetoclax in response to treatment with venetoclax, tedizolid, or combination of the 2 drugs.

2019-08-20 | GSE136032 | GEO

FOXM1-AKT positive regulation loop provides venetoclax resistance in AML

Project description:FOXM1 and AKT are crucial pro-oncogenic regulators of cancer therapy resistance. Due to reciprocal regulatory links they establish a positive feedback autoregulation loop in AML cells. Disruption of this loop via inhibition of either FOXM1 or AKT results in similar gene expression changes, drastic upregulation of HOXA genes and sensitization of AML cells to cytarabine and venetoclax treatment.

2021-08-18 | GSE172189 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data