Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Targeted nanopore sequencing for the identification of ABCB1 promoter translocations in relapsed acute myeloid leukemia [ChIP-seq]

ABSTRACT: Resistance to chemotherapy is the most common cause of treatment failure in acute myeloid leukemia and the drug efflux pump ABCB1 is a critical mediator. Here we demonstrate that in vitro daunorubicin exposure can induce activating ABCB1 promoter translocations in human myeloid cells, similar to those recently described in recurrent high-grade serous ovarian and breast cancer. We then develop a targeted nanopore sequencing approach that enables efficient identification of ABCB1 structural variants in high-grade serous ovarian cancer. Finally, we confirm that ABCB1high cases of relapsed AML are not characterized by ABCB1 promoter translocations but instead show high-level activity of native promoters, consistent with endogenous regulation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE159317 | GEO | 2020/10/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Targeted nanopore sequencing for the identification of ABCB1 promoter translocations in relapsed acute myeloid leukemia [RNAseq]

Project description:Resistance to chemotherapy is the most common cause of treatment failure in acute myeloid leukemia and the drug efflux pump ABCB1 is a critical mediator. Here we demonstrate that in vitro daunorubicin exposure can induce activating ABCB1 promoter translocations in human myeloid cells, similar to those recently described in recurrent high-grade serous ovarian and breast cancer. We then develop a targeted nanopore sequencing approach that enables efficient identification of ABCB1 structural variants in high-grade serous ovarian cancer. Finally, we confirm that ABCB1high cases of relapsed AML are not characterized by ABCB1 promoter translocations but instead show high-level activity of native promoters, consistent with endogenous regulation.

2020-10-22 | GSE159391 | GEO

Targeted nanopore sequencing for the identification of ABCB1 promoter translocations in relapsed acute myeloid leukemia [Nanopore]

2020-10-22 | GSE159324 | GEO

Targeted nanopore sequencing for the identification of ABCB1 promoter translocations in relapsed acute myeloid leukemia [4C-seq]

2020-10-22 | GSE159394 | GEO

Targeted nanopore sequencing for the identification of ABCB1 promoter translocations in relapsed acute myeloid leukemia [Targeted Resequencing]

2020-10-22 | GSE159331 | GEO

E-GEOD-14001

Project description:Transcription profiling by array of human high and low grade ovarian serous carcinomas

2025-01-24 | E-GEOD-14001 | ExpressionAtlas

E-GEOD-40595

Project description:A cancer associated fibroblasts (CAFs) specific gene signature in high grade serous ovarian cancer

2025-01-24 | E-GEOD-40595 | ExpressionAtlas

E-MTAB-7083

Project description:Transcriptional profiling of platinum sensitive and platinum resistant high grade serous ovarian cancer samples

2025-01-23 | E-MTAB-7083 | ExpressionAtlas

Phenotypic consequences of SLC25A40-ABCB1 fusions beyond drug resistance in High Grade Serous Ovarian Cancer

Project description:Phenotypic consequences of SLC25A40-ABCB1 fusions beyond drug resistance in High Grade Serous Ovarian Cancer

| PRJNA759615 | ENA

Phenotypic consequences of SLC25A40-ABCB1 fusions beyond drug resistance in High Grade Serous Ovarian Cancer

Project description:Purpose: Our laboratory recently identified the most common mechanism of acquired drug resistance in High Grade Serous Ovarian Cancer (HGSOC) to date, SLC25A40-ABCB1 fusions. The primary aim of this study was to examine the transcriptional profile of drug resistant fusion-positive SLC25A40-ABCB1 fusion positive cells. Single cell fusion-positive and negative clones were derived from the human HGSOC cell line AOCS-18.5 Methods: Three independent replicates of RNA was collected from five SLC25A40-ABCB1 fusion-negative AOCS 18.5 clones (B,C, D,E,F) and five SLC25A40-ABCB1 fusion-positive AOCS 18.5 clones (8,9,13, 15B, 18B) and submitted for NextSeq 100bp paired-end, polyA RNA-sequencing. Cells were collected 48-72hrs post seeding. 20 million paired end reads per sample were generated. Reads were mapped to the human reference GRCh37.92 using the STAR two pass method (v2.6.0b). Counts were generated on the ensemble release GRCh37.92 GTF annotation using HTSeq (v0.10.0). Counts were normalized to logged TMM values using edgeR (v3.28.1). TPM expression values were also generated. Differential gene expression analysis was performed using DESeq2 (v1.26.0) on the raw counts. In all, 3333 genes were significantly upregulated (>1.5 log2 fold change, p-adj<0.1) in fusion-positive lines, with 1751 genes significantly downregulated Conclusions: Using a stringent cut-off of >2.0 fold change (n=2238 differentially expressed genes), Metascape pathway analysis revealed that the most significantly enriched pathways in fusion-positive clones included the NABA matrisome associated pathway (160/751 genes, 7.24%), followed by external encapsulating structure organization (102/398 genes, 4.62%) and regulation of cell adhesion (139/734 genes, 6.29%).

2021-09-03 | GSE183210 | GEO

Dynamic induction of drug resistance through a stress-responsive enhancer in acute myeloid leukemia [RNA-seq]

Project description:The drug efflux pump ABCB1 is a key driver of chemoresistance, and high expression predicts for treatment failure in acute myeloid leukemia (AML). We show that both acute and chronic exposure of leukemia cells to daunorubicin activates an integrated stress response-like transcriptional program to induce ABCB1 through remodeling and dynamic activation of an ATF4-bound, stress-responsive enhancer. In primary human AML, stress-responsive ABCB1 enhancers are accessible and acetylated, and exposure of fresh blast cells to daunorubicin induces ABCB1 in a dose-dependent manner. Dynamic induction of ABCB1 by diverse stressors, including chemotherapy, facilitates escape of leukemia cells from targeted third-generation ABCB1 inhibition. Stress-induced up regulation of ABCB1 is mitigated by combined use of pharmacologic inhibitors U0126 and ISRIB, which inhibit stress signaling.

2020-02-03 | GSE131823 | 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