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Transcriptional adaptation and enhancer rewiring promote metabolic resistance in BRAFmutated multiple myeloma (scRNA-seq)

ABSTRACT: Transcriptional adaptation and enhancer rewiring promote metabolic resistance in BRAFmutated multiple myeloma (scRNA-seq)

PROVIDER: PRJNA714650 | ENA |

REPOSITORIES: ENA

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Transcriptional adaptation and enhancer rewiring promote metabolic resistance in BRAFmutated multiple myeloma

Project description:Transcriptional adaptation and enhancer rewiring promote metabolic resistance in BRAFmutated multiple myeloma

| PRJNA714647 | ENA

Transcriptional adaptation and enhancer rewiring promote metabolic resistance in BRAFmutated multiple myeloma (ChIP-seq)

Project description:Purpose: We examined the mechanisms of transcriptional adaptation in persistent cells and asked if transcriptional state changes can be attributed to alterations in enhancer activity. Methods: ChIPseq for the enhancer mark H3K27ac was performed in three single-cell clones derived from the multiple myeloma cell line U266 treted with dabrafenib vs. DMSO for 14 Results: We observed substantial epigenetic remodeling illustrated by a greater number of unique peaks in dabrafenib-persistent cells as compared to dabrafenib-naïve controls. Out of a total of 22756 merged peaks, which were called in at least three samples, 7645 (34%) were unique to persistent cells compared to 454 (2%) in untreated cells. Conclusions: Altered transcriptional states are associated with enhancer rewiring in drug-resistant myeloma

2022-03-13 | GSE168949 | GEO

Transcriptional adaptation and enhancer rewiring promote metabolic resistance in BRAFmutated multiple myeloma (scRNA-seq)

Project description:Transcriptional adaptation and enhancer rewiring promote metabolic resistance in BRAFmutated multiple myeloma (scRNA-seq)

| PRJNA714650 | ENA

Transcriptional adaptation and enhancer rewiring promote metabolic resistance in BRAFmutated multiple myeloma (ChIP-seq)

Project description:Transcriptional adaptation and enhancer rewiring promote metabolic resistance in BRAFmutated multiple myeloma (ChIP-seq)

| PRJNA714651 | ENA

Transcriptional adaptation and enhancer rewiring promote metabolic resistance in BRAFmutated multiple myeloma (bulkRNA-seq)

Project description:Transcriptional adaptation and enhancer rewiring promote metabolic resistance in BRAFmutated multiple myeloma (bulkRNA-seq)

| PRJNA714652 | ENA

Transcriptional adaptation and enhancer rewiring promote metabolic resistance in BRAFmutated multiple myeloma (scRNA-seq)

Project description:Purpose: We here applied single-cell RNA sequencing of circulating MM cells from primary MM patients to perform transcriptional profiling of myeloma cells and study emerging resistance mechanisms in real-time. Methods: A total of 1509 single CD138+/CD38+ myeloma and normal plasma cells from three patients and one normal donor were examined by full-length single-cell RNA sequencing. Results: Quality filtering resulted in the retention of 1153 cells with an average of 4836 genes detected per cell. Rapid transcriptional adaptation was observed in the presence of BRAF/MEK inhibitor treatment. Conclusions: Inhibition of the BRAF/MEK pathway in myeloma patients induces cellular adaptation accompanied by metabolic resistance and preferential transcriptional activation of OxPhos.

2022-03-13 | GSE168948 | GEO

Transcriptional adaptation and enhancer rewiring promote metabolic resistance in BRAFmutated multiple myeloma (bulkRNA-seq)

Project description:Purpose: We examined how transcriptional state changes relate to clonal selection as BRAF inhibitor resistance develops in BRAF-mutated myeloma. Methods: To this end we generated three single-cell clones from U266, a BRAFK601N -mutated myeloma cell line and DP6- a BRAFV600E myeloma cell line. All three U266 and DP6 clones were subjected to long-term dabrafenib treatment at their established IC50 doses (U266: 10uM, DP6 1nM). Bulk RNA-seq was performed before treatment, day 7, day 14, day 42 and at time of resistance. Results: Transcriptional adaptation after seven days was homogeneous for all clones, but was different across both cell lines. Oxidative phosphorylation (OxPhos) emerged as the most consistently enriched signaling pathway in persistent cells from both cell lines as compared to baseline. Conclusions: BRAF inhibition in BRAF-mutated myeloma cells leads to transcriptional reprogramming with induction of OxPhos-related genes within a brief period of time.

2022-03-13 | GSE168950 | GEO

Transcriptional adaptation and enhancer rewiring promote metabolic resistance in BRAFmutated multiple myeloma

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-03-13 | GSE168951 | GEO

Targeting DNA2 Overcomes Metabolic Reprogramming in Multiple Myeloma

Project description:Targeting DNA2 is synthetically lethal in myeloma cells that undergo metabolic adaptation and rely on oxidative phosphorylation to maintain survival after DNA damage activation.

2023-11-27 | GSE196766 | GEO

Multiple myeloma

Project description:Multiple myeloma

| PRJNA515992 | ENA