This SuperSeries is composed of the SubSeries listed below.
Targeting c-FOS and DUSP1 abrogates intrinsic resistance to tyrosine-kinase inhibitor therapy in BCR-ABL-induced leukemia.
Specimen part, Cell line
View SamplesThe Baf3 are dependent on IL-3 for grwoth however transformation by BCR -ABL oncogene causes BAf3 cells independent of IL-3. The BAf3 cells expressing BCR-ABL are dependent on continuous expression of BCR_ABL for growth. Inhibitionof BCR-ABL by its inhibitor Imatinib cause these cells to undergo apoptosis. When these cells are grown with IL-3 these cells do not respond to Imatinib mediated grwoth arrest.
Targeting c-FOS and DUSP1 abrogates intrinsic resistance to tyrosine-kinase inhibitor therapy in BCR-ABL-induced leukemia.
Cell line
View SamplesK562 cells when grown with erythropeitin do not respond to Imatinib. Here we are comparing the gene expression profile from imatinib resistant and sensitive cells.
Targeting c-FOS and DUSP1 abrogates intrinsic resistance to tyrosine-kinase inhibitor therapy in BCR-ABL-induced leukemia.
Cell line
View SamplesBAF3 cells harboring constitutively expressing BCR-ABL were grown with or without IL-3 supplement and treated with Imatinib and live cells from the IL-3 and without IL-3 were sorted by FACS.
Targeting c-FOS and DUSP1 abrogates intrinsic resistance to tyrosine-kinase inhibitor therapy in BCR-ABL-induced leukemia.
Cell line
View SamplesObjective: A multi-center study of recent onset juvenile idiopathic arthritis (JIA) subjects prior to treatment with DMARDS or biologics was undertaken to identify peripheral blood gene expression differences between JIA subclasses and controls. Methods: PBMC from 59 healthy children and 136 JIA subjects (28 enthesitis-related arthritis[ERA], 42 persistent oligoarthritis, 45 RF- polyarthritis, and 21 systemic) were isolated on Ficoll. Poly-A RNA was labeled using NuGEN Ovation and gene expression profiles were obtained using Affymetrix HG-U133 plus 2.0 Arrays. Results: 9,501 differentially expressed probe sets were identified among JIA subtypes and controls (ANOVA, FDR 5%). Specifically, 193, 1036, 873 and 7595 probe sets were different between controls and ERA, persistent oligoarthritis, RF- polyarthritis and systemic JIA samples respectively. In persistent oligoarthritis, RF- polyarthritis and systemic JIA subtypes, up-regulation of gene associated with IL-10 signaling was prominent. A hemoglobin cluster was identified that was under-expressed in ERA patients but over-expressed in systemic JIA. The influence of JAK/STAT, ERK/MAPK, IL-2 and B cell receptor signaling pathways was evident in persistent oligoarthritis. In systemic JIA, up regulation of innate immune pathways, including IL-6, TLR/IL1R, and PPAR signaling were noted, along with down regulation of gene networks related to NK and T cells. Complement and coagulation pathways were up-regulated in systemic JIA with a subset of these components differentially-expressed in the other three subtypes. Conclusions: Expression analysis identified differentially expressed genes in PBMCs between subclasses of JIA early in disease and controls, thus providing evidence for immunobiologic differences between these forms of childhood arthritis.
Subtype-specific peripheral blood gene expression profiles in recent-onset juvenile idiopathic arthritis.
Sex, Specimen part, Race
View SamplesObjective. To identify gene expression differences in peripheral blood from patients with early and late onset juvenile idiopathic arthritis (JIA).
Biologic similarities based on age at onset in oligoarticular and polyarticular subtypes of juvenile idiopathic arthritis.
Sex, Specimen part, Race
View SamplesObjective. Previous observations suggest that active systemic juvenile idiopathic arthritis (sJIA) is associated with a prominent erythropoiesis gene expression signature. The aim of this study was to determine the association of this signature with peripheral blood mononuclear cell (PBMC) subpopulations and its specificity for sJIA as compared to related conditions.
Immature cell populations and an erythropoiesis gene-expression signature in systemic juvenile idiopathic arthritis: implications for pathogenesis.
Sex, Specimen part, Race
View SamplesObjective. Microarray analysis was used to determine whether children with recent onset polyarticular juvenile idiopathic arthritis (JIA) exhibit biologically or clinically informative gene expression signatures in peripheral blood mononuclear cells (PBMC). Methods. Peripheral blood samples were obtained from 59 healthy children and 61 children with polyarticular JIA prior to treatment with second-line medications, such as methotrexate or biological agents. RNA was purified from Ficoll-isolated mononuclear cells, fluorescently labeled and then hybridized to Affymetrix U133 Plus 2.0 GeneChips. Data were analyzed using ANOVA at a 5% false discovery rate threshold after Robust Multi-Array Average pre-processing and Distance Weighted Discrimination normalization. Results. Initial analysis revealed 873 probe sets for genes that were differentially expressed between polyarticular JIA and controls. Hierarchical clustering of these probe sets distinguished three subgroups within polyarticular JIA. Prototypical subjects within each subgroup were identified and used to define subgroup-specific gene expression signatures. One of these signatures was associated with monocyte markers, another with transforming growth factor-beta-inducible genes, and a third with immediate-early genes. Correlation of these gene expression signatures with clinical and biological features of JIA subgroups suggests direct relevance to aspects of disease activity and supports the division of polyarticular JIA into distinct subsets. Conclusions. PBMC gene expression signatures in recent onset polyarticular JIA reflect discrete disease processes and offer a molecular classification of disease.
Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets.
Sex, Specimen part, Race
View SamplesJuvenile idiopathic arthritis (JIA) is the most common chronic childhood rheumatic disease in the Western world. To identify novel JIA predisposing loci, a genome-wide association study (GWAS) in 814 Caucasian JIA cases and 3058 Caucasian controls was completed. After adjusting for the most significant HLA associations, the strongest novel associations included rs6479891 (10q21, odds ratio (OR)=1.59, P=1.3x10-8) and rs10761747 (OR=1.34, P=4.0x10-5) within JMJD1C; rs12719740 (15q26, OR=1.47, P=3.3x10-7) near FAM169B; rs4688011 (3q13, OR=1.33, P=1.1x10-4) within C3orf1 and rs4254850 (4q31, OR=0.85, P=7.8x10-3) near IL15. Eleven SNPs were genotyped in Caucasian replication cohorts (1744 cases, 7010 controls) and meta-analysis continued to provide evidence for association with three of the SNPs (rs6479891, P=4.3x10-5; rs12719740, P=5.2x10-4; rs4688011, P=3.6x10-7). Analysis of expression data from 68 JIA cases and 23 controls overlapping in the GWAS cohort1 and published lymphoblastoid cell lines (LCL)2 showed cis eQTL associations for JMJD1C SNPs (P=0.01 and P=1.6x10-6, respectively), and the C3orf1 SNP (P=5.7x10-6).
Genome-wide association analysis of juvenile idiopathic arthritis identifies a new susceptibility locus at chromosomal region 3q13.
Sex, Specimen part, Disease, Disease stage, Race
View SamplesBiotinylated cRNA was synthesized from total RNA (Enzo; Farmingdale, NY) and processed according to the Affymetrix GeneChip Expression Analysis Technical Manual (Affymetrix; Santa Clara, CA). 57 samples: 5 pauciarticular PBMC, 15 polyarticular PBMC, 11 control PMBC, 6 JSpA PBMC, 5 pauciarticular SFMC, 10 polyarticular PBMC, 5 JSpA SFMC classified by course.
Gene expression in juvenile arthritis and spondyloarthropathy: pro-angiogenic ELR+ chemokine genes relate to course of arthritis.
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