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Molecular characterization stratifies VQ myeloma cells into two clusters with distinct risk signatures and drug responses

ABSTRACT: Molecular characterization stratifies VQ myeloma cells into two clusters with distinct risk signatures and drug responses

PROVIDER: PRJNA941848 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23721300.fastq.gz	Fastqsanger.gz
	SRR23719901_1.fastq.gz	Fastqsanger.gz
	SRR23719901_2.fastq.gz	Fastqsanger.gz
	SRR23721301.fastq.gz	Fastqsanger.gz
	SRR23719902_1.fastq.gz	Fastqsanger.gz

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Molecular characterization stratifies VQ myeloma cells into two clusters with distinct risk signatures and drug responses [Repertoire-Seq]

Project description:Multiple myeloma (MM) is a cancer of malignant plasma cells in the bone marrow and extramedullary sites. We previously characterized a VQ model for human high-risk MM. Different VQ lines display distinct disease phenotypes and survivals, suggesting significant intra-model variation. Here, we use whole exome sequencing and copy number variation (CNV) analysis coupled with RNA-Seq to stratify VQ lines into corresponding clusters: Group A cells had monosomy chr5 and overexpressed genes and pathways associated with sensitivity to bortezomib (Btz) treatment in human MM patients. By contrast, Group B VQ cells carried recurrent amplification (Amp) of chromosome (chr) 3 and displayed high-risk MM features, including downregulation of Fam46c, upregulation of cancer growth pathways associated with functional high-risk MM, and expression of Amp1q and high-risk UMAS-70 and EMC-92 gene signatures. Consistently, in sharp contrast to Group A VQ cells that showed short-term response to Btz, Group B VQ cells were de novo resistant to Btz in vivo. Our study highlights Group B VQ lines as highly representative of the human MM subset with ultrahigh risk.

2023-04-04 | GSE226830 | GEO

Molecular characterization stratifies VQ myeloma cells into two clusters with distinct risk signatures and drug responses [RNA-Seq]

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Molecular characterization stratifies VQ myeloma cells into two clusters with distinct risk signatures and drug responses [RNA-Seq]

Project description:Molecular characterization stratifies VQ myeloma cells into two clusters with distinct risk signatures and drug responses [RNA-Seq]

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Molecular characterization stratifies VQ myeloma cells into two clusters with distinct risk signatures and drug responses [Repertoire-Seq]

Project description:Molecular characterization stratifies VQ myeloma cells into two clusters with distinct risk signatures and drug responses [Repertoire-Seq]

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Molecular characterization stratifies VQ myeloma cells into two clusters with distinct risk signatures and drug responses

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2023-04-04 | GSE226833 | GEO

Molecular characterization stratifies VQ myeloma cells into two clusters with distinct risk signatures and drug responses.

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Project description:Molecular characterization stratifies VQ myeloma cells into two clusters with distinct risk signatures and drug responses

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Single-cell RNAseq of VQ myeloma cells reveals unique transcriptional signatures from normal plasma cells

Project description:NRAS Q61 mutations are prevalent in advanced/relapsed multiple myeloma (MM) and correlate with poor patient outcomes. Thus, we generated a novel MM model by conditionally activating expression of endogenous NrasQ61R and a MYC transgene in germinal center B cells (VQ mice). VQ mice developed a highly malignant MM characterized by high proliferation index, hyperactivation of ERK and AKT signaling, impaired hematopoiesis, widespread extramedullary disease, bone lesions, kidney abnormalities, preserved PD1 and TIGIT immune checkpoint pathways, and expression of human high-risk MM gene signatures. VQ MM mice recapitulate most of the biological and clinical features of human advanced/high-risk MM. These MM phenotypes are serially transplantable in syngeneic recipients. Two MM cell lines were also derived to facilitate future genetic manipulations. Combination therapies based on MEK inhibition significantly prolonged the survival of VQ mice with advanced stage MM. Our study provides a strong rationale to develop MEK inhibition-based therapies for treating advanced/relapsed MM.

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Transcriptomic profiling of normal plasma cells and MM models using bulk RNA-Seq

2020-07-02 | GSE153626 | GEO