Dataset Information

Genome-wide transcriptomics leads to the identification of deregulated genes after deferasirox therapy in low-risk MDS patients

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE141958 | GEO | 2019/12/13

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:Neuroblastoma (NB) is the most frequent extracranial solid tumour of childhood. Clinical courses are highly variable, ranging from spontaneous regression/maturation to rapid progression despite intensive multimodal therapy. The estimation of 5-year event free survival in high-risk patients of only about 40 % stresses an importance of novel therapeutic strategies. A number of iron chelators have demonstrated marked in vitro and in vivo anti-tumor activity and are currently being developed as novel anti-cancer agents. Therefore, the potential antitumor effect of iron chelators in NB cancer was investigated. Among the compounds tested, ciclopirox olamine (CPX) was shown to be one of the most effective intracellular iron chelators in NB cells. To unveil the molecular mechanisms underlying the effects of CPX on viability of NB cells, microarray analysis was performed in CHP134 control cells and cells treated with 5 M-BM-5M CPX for 90 minutes. Inclusion of both total RNA (reflecting transcriptional status of the cells) and polysomal RNA (approximating the proteomic representation of the cells) provided us with a deeper understanding of changes in the cells upon CPX treatment. Keywords: ciclopirox olamine, iron chelator, neuroblastoma, translatome profiling, transcriptome profiling. Keywords: ciclopirox olamine, iron chelator, neuroblastoma, translatome profiling, transcriptome profiling, polysomal profiling, polysomal RNA, translational control, translational profiling, polysome profiling Microarray analysis was performed to enable a comprehensive view of the changes in the transcriptional and translational status of the cells in response to the treatment with an iron chelator CPX. Polysomal RNA and total RNA were isolated from vehicle-treated CHP134 cells and CHP134 cells treated with 5 M-BM-5M CPX for 90 minutes. Each condition is represented by three biological replicates, i.e. the experiment was repeated starting each time from cells seeding yielding an independent RNA sample. In total, 12 samples corresponding to 4 conditions were subjected to microarray analysis.

Dataset Information

Genome-wide transcriptomics leads to the identification of deregulated genes after deferasirox therapy in low-risk MDS patients

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure