cFos Mediates cAMP-Dependent Generation of ROS and Rescue of Maturation Program in Retinoid-Resistant Acute Promyelocytic Leukemia Cell Line NB4-LR1

Carrier, Jean-Luc; Javadi, Pasha; Bourrier, Emilie; Camus, Celine; Ségal-Bendirdjian, Évelyne; Karniguian, A.

doi:10.1371/journal.pone.0050408

Cited by 3 publications

(2 citation statements)

References 29 publications

(31 reference statements)

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“…In our study, these TFs were co-expressed with the highest number of lncRNAs including lncRNA HCG4P7 . HCG4P7 is reportedly as an important immune regulatory molecule [34] and highly co-expressed with the gene encoding leukemia regulator FOS [35]. These networks could provide a valuable resource for investigating the transcriptional regulatory relationships involved in the effect of CD19-CAR-T therapy on B-ALL.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome and Regulatory Network Analyses of CD19-CAR-T Immunotherapy for B-ALL

Zhang¹,

Hu²,

Chen³

et al. 2019

Genomics, Proteomics &Amp; Bioinformatics

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Chimeric antigen receptor (CAR) T cell therapy has exhibited dramatic anti-tumor efficacy in clinical trials. In this study, we reported the transcriptome profiles of bone marrow cells in four B cell acute lymphoblastic leukemia ( B-ALL ) patients before and after CD19-specific CAR-T therapy. CD19-CAR-T therapy remarkably reduced the number of leukemia cells, and three patients achieved bone marrow remission (minimal residual disease negative). The efficacy of CD19-CAR-T therapy on B-ALL was positively correlated with the abundance of CAR and immune cell subpopulations, e.g. , CD8 + T cells and natural killer (NK) cells, in the bone marrow. Additionally, CD19-CAR-T therapy mainly influenced the expression of genes linked to cell cycle and immune response pathways, including the NK cell mediated cytotoxicity and NOD-like receptor signaling pathways. The regulatory network analyses revealed that microRNAs ( e.g. , miR-148a-3p and miR-375), acting as oncogenes or tumor suppressors, could regulate the crosstalk between the genes encoding transcription factors (TFs; e.g. , JUN and FOS ) and histones ( e.g. , HIST1H4A and HIST2H4A ) involved in CD19-CAR-T therapy. Furthermore, many long non-coding RNAs showed a high degree of co-expression with TFs or histones ( e.g. , FOS and HIST1H4B ) and were associated with immune processes. These transcriptome analyses provided important clues for further understanding the gene expression and related mechanisms underlying the efficacy of CAR-T immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Transcriptome and Regulatory Network Analyses of CD19-CAR-T Immunotherapy for B-ALL

Zhang¹,

Hu²,

Chen³

et al. 2019

Genomics, Proteomics &Amp; Bioinformatics

View full text Add to dashboard Cite

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“…PNPT1 is predominantly localized in the mitochondrial inter-membrane space and is implicated in RNA targeting to human mitochondria, small noncoding nuclear RNAs (5S rRNA, MRP RNA, some tRNAs, and miRNAs) [ 64 ]. cAMP-induced cFos is a transcriptional repressor of CD44 that triggers ROS generation [ 65 ]. Additionally, some hub genes found exclusively in SZP have been associated to neuronal plasticity and different cancers, most of them associated to cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Co-expression network of neural-differentiation genes shows specific pattern in schizophrenia

et al. 2015

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BackgroundSchizophrenia is a neurodevelopmental disorder with genetic and environmental factors contributing to its pathogenesis, although the mechanism is unknown due to the difficulties in accessing diseased tissue during human neurodevelopment. The aim of this study was to find neuronal differentiation genes disrupted in schizophrenia and to evaluate those genes in post-mortem brain tissues from schizophrenia cases and controls.MethodsWe analyzed differentially expressed genes (DEG), copy number variation (CNV) and differential methylation in human induced pluripotent stem cells (hiPSC) derived from fibroblasts from one control and one schizophrenia patient and further differentiated into neuron (NPC). Expression of the DEG were analyzed with microarrays of post-mortem brain tissue (frontal cortex) cohort of 29 schizophrenia cases and 30 controls. A Weighted Gene Co-expression Network Analysis (WGCNA) using the DEG was used to detect clusters of co-expressed genes that werenon-conserved between adult cases and controls brain samples.ResultsWe identified methylation alterations potentially involved with neuronal differentiation in schizophrenia, which displayed an over-representation of genes related to chromatin remodeling complex (adjP = 0.04). We found 228 DEG associated with neuronal differentiation. These genes were involved with metabolic processes, signal transduction, nervous system development, regulation of neurogenesis and neuronal differentiation. Between adult brain samples from cases and controls there were 233 DEG, with only four genes overlapping with the 228 DEG, probably because we compared single cell to tissue bulks and more importantly, the cells were at different stages of development. The comparison of the co-expressed network of the 228 genes in adult brain samples between cases and controls revealed a less conserved module enriched for genes associated with oxidative stress and negative regulation of cell differentiation.ConclusionThis study supports the relevance of using cellular approaches to dissect molecular aspects of neurogenesis with impact in the schizophrenic brain. We showed that, although generated by different approaches, both sets of DEG associated to schizophrenia were involved with neocortical development. The results add to the hypothesis that critical metabolic changes may be occurring during early neurodevelopment influencing faulty development of the brain and potentially contributing to further vulnerability to the illness.Electronic supplementary materialThe online version of this article (doi:10.1186/s12920-015-0098-9) contains supplementary material, which is available to authorized users.

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New synergistic combinations of differentiation-inducing agents in the treatment of acute promyelocytic leukemia cells

et al. 2018

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cFos Mediates cAMP-Dependent Generation of ROS and Rescue of Maturation Program in Retinoid-Resistant Acute Promyelocytic Leukemia Cell Line NB4-LR1

Cited by 3 publications

References 29 publications

Transcriptome and Regulatory Network Analyses of CD19-CAR-T Immunotherapy for B-ALL

Transcriptome and Regulatory Network Analyses of CD19-CAR-T Immunotherapy for B-ALL

Co-expression network of neural-differentiation genes shows specific pattern in schizophrenia

New synergistic combinations of differentiation-inducing agents in the treatment of acute promyelocytic leukemia cells

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