The iron chelator deferasirox is widely used in patients with iron overload. Patients with low-grade myelodysplastic syndromes (MDS) get transfusion dependency and need to be treated with deferasirox to avoid iron overload. Moreover, in some patients an increase in both erythroid and platelets have been observed after deferasirox therapy. However, the mechanisms involved in these clinical findings are poorly understood. The aim of this work was to analyze, in patients treated with deferasirox, the changes in the gene expression profile after receiving the treatment. A total of fifteen patients with the diagnosis of low-grade MDS were studied. Microarrays were carried out in RNA from peripheral blood before and after 14 weeks of deferasirox therapy. Changes in 1,457 genes and 54 miRNAs were observed: deferasirox induced the downregulation of genes related to the Nf kB pathway leading of an overall inactivation of this pathway. In addition, the iron chelator also downregulated gamma interferon. Altogether these changes could be related to the improvement of erythroid response observed in these patients after therapy. Moreover, the inhibition of NFE2L2/ NRF2, which was predicted in silico, could be playing a critical role in the reduction of reactive oxygen species (ROS). Of note, miR-125b, overexpressed after deferasirox treatment, could be involved in the reduced inflammation and increased hematopoiesis observed in the patients after treatment. In summary this study shows, for the first time, the mechanisms that could be governing deferasirox impact in vivo.
Genome-wide transcriptomics leads to the identification of deregulated genes after deferasirox therapy in low-risk MDS patients.
Specimen part, Disease, Treatment, Subject
View SamplesIn Arabidposis thaliana, the msh1 recA3 double mutant shows an extensive mitochondrial genome rearrangement and displays pronounced thermotolerance.
Extensive rearrangement of the Arabidopsis mitochondrial genome elicits cellular conditions for thermotolerance.
Specimen part
View SamplesSingle mutant msh1
Extensive rearrangement of the Arabidopsis mitochondrial genome elicits cellular conditions for thermotolerance.
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View SamplesDouble mutant msh1 and recA3
Extensive rearrangement of the Arabidopsis mitochondrial genome elicits cellular conditions for thermotolerance.
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View SamplesThe soybean msh1 RNAi transgenic line show various growth phenotype. We use microarray analysis to characterize gene expression pattern for two of the phenotypes - variegation and stunted growth.
MutS HOMOLOG1 is a nucleoid protein that alters mitochondrial and plastid properties and plant response to high light.
Specimen part
View SamplesThe soybean msh1 RNAi transgenic line show various growth phenotype. We use microarray analysis to characterize gene expression pattern for two of the phenotypes - variegation and stunted growth.
MutS HOMOLOG1 is a nucleoid protein that alters mitochondrial and plastid properties and plant response to high light.
Specimen part
View SamplesThe Arabidopsis msh1 mutant show various growth phenotype. We use microarray analysis to characterize gene expression pattern for two of the phenotypes - variegation and stunted growth.
The chloroplast triggers developmental reprogramming when mutS HOMOLOG1 is suppressed in plants.
Specimen part
View SamplesStem and progenitor cells maintain the tissue they reside in for life by regulating the balance between proliferation and differentiation. How this is done is not well understood. Here, we report that DDX6 is necessary for maintaining human epidermal progenitor cell self-renewal.
DDX6 Orchestrates Mammalian Progenitor Function through the mRNA Degradation and Translation Pathways.
Specimen part
View SamplesWe used microarrays to investigate gene expression changes in the pancreas of RasGrf1 KO mice. These animals have a reduction in the number and size of the pancreatic islets which lead to lower levels of insulin and glucagon in their blood.
Transcriptional profiling reveals functional links between RasGrf1 and Pttg1 in pancreatic beta cells.
Specimen part
View SamplesWe used microarrays to expression profile peripheral blood mononuclear cells (PBMCs) from LGL leukemia patients and control subjects to identify survival pathways that render leukemic LGL resistant to activation induced cell death.
Molecular profiling of LGL leukemia reveals role of sphingolipid signaling in survival of cytotoxic lymphocytes.
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