Gene Set: JISON_SICKLE_CELL_DISEASE_DN

Standard name JISON_SICKLE_CELL_DISEASE_DN
Systematic name M4911
Brief description Genes down-regulated in peripheral blood mononuclear cells (PBMC) from sickle cell disease patients compared to those from healthy subjects.
Full description or abstract In sickle cell disease, deoxygenation of intra-erythrocytic hemoglobin S leads to hemoglobin polymerization, erythrocyte rigidity, hemolysis, and microvascular occlusion. Ischemia-reperfusion injury, plasma hemoglobin-mediated nitric oxide consumption, and free radical generation activate systemic inflammatory responses. To characterize the role of circulating leukocytes in sickle cell pathogenesis we performed global transcriptional analysis of blood mononuclear cells from 27 patients in steady-state sickle cell disease (10 patients treated and 17 patients untreated with hydroxyurea) compared with 13 control subjects. We used gender-specific gene expression to validate human microarray experiments. Patients with sickle cell disease demonstrated differential gene expression of 112 genes involved in heme metabolism, cell-cycle regulation, antioxidant and stress responses, inflammation, and angiogenesis. Inducible heme oxygenase-1 and downstream proteins biliverdin reductase and p21, a cyclin-dependent kinase, were up-regulated, potentially contributing to phenotypic heterogeneity and absence of atherosclerosis in patients with sickle cell disease despite endothelial dysfunction and vascular inflammation. Hydroxyurea therapy did not significantly affect leukocyte gene expression, suggesting that such therapy has limited direct anti-inflammatory activity beyond leukoreduction. Global transcriptional analysis of circulating leukocytes highlights the intense oxidant and inflammatory nature of steady-state sickle cell disease and provides insight into the broad compensatory responses to vascular injury.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 15031206   Authors: Jison ML,Munson PJ,Barb JJ,Suffredini AF,Talwar S,Logun C,Raghavachari N,Beigel JH,Shelhamer JH,Danner RL,Gladwin MT
Exact source Table 1S: fold change < 1
Related gene sets (show 1 additional gene sets from the source publication)

(show 27 gene sets from the same authors)
External links  
Filtered by similarity
Organism Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
Source platform AFFY_HG_U95
Dataset references  
Download gene set format: grp | text | gmt | gmx | xml
Compute overlaps (show collections to investigate for overlap with this gene set)
Compendia expression profiles GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
Advanced query Further investigate these 187 genes
Gene families Categorize these 187 genes by gene family
Show members (show 196 members mapped to 187 genes)
Version history  

See MSigDB license terms here. Please note that certain gene sets have special access terms.