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Genome-scale CRISPR screen identifies nucleotide metabolism as an actionable therapeutic vulnerability in diffuse large B-cell lymphoma [RNA-seq]

ABSTRACT: Myc dysregulation underpins lymphomagenesis in the Atm-null DLBCL model and confers dependence on nucleotide biosynthesis.MYC-driven DLBCL is sensitive to nucleotide depletion with combined mycophenolate mofetil and adavosertib in vitro and in vivo.

ORGANISM(S): Mus musculus

PROVIDER: GSE215222 | GEO | 2022/10/16

REPOSITORIES: GEO

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Genome-scale CRISPR screen identifies nucleotide metabolism as an actionable therapeutic vulnerability in diffuse large B-cell lymphoma [CRISPR sgRNA]

Project description:Myc dysregulation underpins lymphomagenesis in the Atm-null DLBCL model and confers dependence on nucleotide biosynthesis.MYC-driven DLBCL is sensitive to nucleotide depletion with combined mycophenolate mofetil and adavosertib in vitro and in vivo.

2022-10-22 | GSE215874 | GEO

Mycophenolate Treatment in Systemic Sclerosis

Project description:Skin gene expression signatures, including intrinsic subset, are associated with improvement during Mycophenolate mofetil (MMF) treatment.

2014-07-25 | GSE59785 | GEO

Molecular Signatures in Skin Associated with Clinical Improvement During Mycophenolate Treatment in Systemic Sclerosis

Project description:Skin gene expression signatures, including intrinsic subset, are associated with skin score/MRSS improvement during mycophenolate mofetil (MMF) treatment.

2013-04-09 | GSE45485 | GEO

ATM-deficient B cell lymphomas

2015-12-09 | GSE68505 | GEO

Mycophenolate Treatment in Systemic Sclerosis

Project description:Skin gene expression signatures, including intrinsic subset, are associated with improvement during Mycophenolate mofetil (MMF) treatment. Longitudinal SSc patient biopsies and controls were integrated into 83 sample dataset totaling 165 arrays for gene expression and analysis

2014-07-25 | E-GEOD-59785 | biostudies-arrayexpress

Transcriptomic analysis uncovers novel synergistic mechanisms in combination therapy for lupus nephritis

Project description:To explore the underlying molecular and cellular mechanisms of increased efficacy of the combination therapy regimen, we employed a mouse model of lupus nephritis, MRL/lpr mice, and treated them with monotherapies of prednisone, mycophenolate mofetil, or tacrolimus, or with their combination. Consistent with previous clinical findings, combination therapy markedly improved renal outcome compared to the monotherapies in mice with lupus nephritis. Transcriptomic analysis of their kidneys revealed distinct molecular pathways that were differentially regulated in combination therapy versus monotherapies. Combination therapy not only provided additive immunosuppressive effects, but also induced gene expression and molecular pathways to confer enhanced renoprotection. Specifically, combination therapy inhibited TLR7 expression in the kidneys of mice with lupus nephritis; combination of tacrolimus and mycophenolate mofetil led to better stabilization of the podocyte actin cytoskeleton through the reciprocal regulation of RhoA and Rac1 activities. Combination therapy strongly suppressed the IL-6/Stat3 pathway. These findings were further validated in renal biopsy samples from patients with lupus nephritis before and after treatments with mycophenolate mofetil, tacrolimus or combination therapy. Thus, our study further supports the earlier clinical finding and further provides insights into the molecular basis for increased efficacy of combination therapy.

2020-06-24 | GSE153021 | GEO

Molecular Signatures in Skin Associated with Clinical Improvement During Mycophenolate Treatment in Systemic Sclerosis

Project description:Skin gene expression signatures, including intrinsic subset, are associated with skin score/MRSS improvement during mycophenolate mofetil (MMF) treatment. Gene expression and intrinsic subset assignment were measured in SSc patients amd controls at baseline, and from biopsies of MMF-treated patients.

2013-04-09 | E-GEOD-45485 | biostudies-arrayexpress

Homo sapiens

Project description:Systemic sclerosis skin disease trajectory during mycophenolate mofetil treatment

| PRJNA308851 | ENA

ATM-deficient B cell lymphomas

Project description:Ataxia-telangiectasia mutated (ATM) kinase plays a central role in maintaining genomic integrity. In both humans and mice, ATM deficiency is associated with an increased incidence of lymphoid cancers that are primarily T cell in origin. We demonstrate here that when T cells are removed as targets for lymphomagenesis and as mediators of immune surveillance, ATM-deficient mice exclusively develop early onset IgM+ B cell lymphomas that by histology and gene expression profiling resemble the activated B cell-like (ABC) subset of human diffuse large B cell lymphomas (DLBCL). These ATM-deficient B cell tumors show considerable chromosomal instability and a recurrent genomic amplification of a 4.48 Mb region on chromosome 18 that contains Malt1 and is orthologous to a region similarly amplified in human ABC-DLBCL. Further, the amplification of Malt1 in these lymphomas correlates with their dependence on NF-kB, MALT1, and BCR signaling for survival, paralleling human ABC-DLBCL. This study reveals that ATM protects against development of B cell lymphomas that model human ABC-DLBCL and identifies a role for T cells in preventing the emergence of these tumors. We performed gene expression profiling on nine ATMKO.CD3epsilonKO lymphoma cell lines (n=12, 3 technical repeats). We analyzed gene expression of anti-IgM stimulated primary B cells from both ATMKO.CD3epsilonKO (n=7, 5 technical repeats) and ATMWT.CD3epsilonKO mice (n=2), and GC B cells isolated from SRBC-immunized ATMWT mice (n=3, 1 biological repeat and 2 technical repeats). We analyzed gene expression following treatment of two ATMKO.CD3epsilonKO lymphoma cell lines with the BTK inhibitor, PCI-32765, at time points (1, 3, 6, and 24 hours) as compared to time points with vehicle (DMSO) (n=8).

2015-12-09 | E-GEOD-68505 | biostudies-arrayexpress

Discovery of novel differentially expressed genes related to interstitial fibrosis and tubular atrophy among kidney transplantation recipients by mRNA-sequencing

Project description:Interstitial fibrosis and tubular atrophy (IF/TA) after kidney transplantation causes chronic deterioration of graft function. IF/TA can be diagnosed by graft biopsy; however, non-invasive diagnostic methods are unavailable. In this study, we identified IF/TA-related differentially expressed genes (DEGs) through next-generation sequencing using peripheral blood mononuclear cells (PBMCs) PBMC samples from kidney transplantation recipients under standard immunosuppressive therapy (tacrolimus/mycophenolate mofetil or mycophenolate sodium/steroid) and diagnosed as IF/TA (n = 41) or normal (controls; n = 41) at their 1-year protocol biopsy were recruited between January 2020 and August 2020.

2023-08-30 | GSE218048 | GEO

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