Metabolomics in AML
Ontology highlight
ABSTRACT:
ORGANISM(S): Human Homo Sapiens
TISSUE(S): Blood
SUBMITTER: 
Jatinder Lamba
PROVIDER: ST000270 | MetabolomicsWorkbench | Thu Aug 27 00:00:00 BST 2015
REPOSITORIES: MetabolomicsWorkbench
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Project description:Punch biopsies of patients enrolled in phase II clinical trial study was obtained at various time points. Skin biopsies from 16 responders and 8 non responders and partial responders, chosen after the completion of clinical trial, was evaluated before Itolizumab treatment (Day 1) and at Day 57. Responders had a PASI improvement >75% while non responders had a PASI improvement <60%. The gene expression values at Day 57 were normalised with values obtained at Day 1 of the respective patient sample. The genes with a minimum fold change of 1.8 spontaneously clustered into predominantly responders and non responders.
2016-09-01 | GSE72246 | GEO
Project description:Punch biopsies of patients enrolled in phase II clinical trial study was obtained at various time points. Skin biopsies from 16 responders and 8 non responders and partial responders, chosen after the completion of clinical trial, was evaluated before Itolizumab treatment (Day 1) and at Day 57. Responders had a PASI improvement >75% while non responders had a PASI improvement <60%. The gene expression values at Day 57 were normalised with values obtained at Day 1 of the respective patient sample. The genes with a minimum fold change of 1.8 spontaneously clustered into predominantly responders and non responders. Agilent Custom Human Gene Expression 8X15k (AMADID: 16332) designed by Genotypic Technology Private Limited .
2016-09-01 | E-GEOD-72246 | biostudies-arrayexpress
Project description:Despite the increasing of available drugs in RA, the overall rate of non response is 30 to 40% of treated patients. To optimize the drug prescription and better elaborate the therapeutic strategies, gene profiling in PBMCs was used to predict the responsiveness to anakinra. Thirty two patients treated by anakinra (100mg/day s.c.) and méthotrexate, were categorized as responders whenever a change of Disease Activity Score 28 > 1.2 was obtained at 3 months. Blood from treated patients was collected at baseline. In 7 responders and 7 non responders, 51 mRNAs identified by microarray were expressed as a function of the response to treatment and an unsupervised hierarchical clustering perfectly separated responders from non responders. Keywords: anakinra effect
2008-06-19 | GSE11827 | GEO
Project description:Background: Immunoadsorption with subsequent IgG substitution (IA/IgG) represents a novel therapeutic approach in treatment of dilated cardiomyopathy (DCM) which leads to improvement of left ventricular ejection fraction (LVEF). However, response to this therapeutic intervention shows wide inter-individual variability. In this pilot study, we tested the value of clinical, biochemical and molecular parameters for prediction of the response of patients with DCM to IA/IgG. Methods & Results: Forty DCM patients underwent endomyocardial biopsies (EMBs) before IA/IgG. In 8 patients with normal LVEF (controls) EMB were obtained for clinical reasons. Clinical parameters, negative inotropic activity (NIA) of antibodies on isolated rat cardiomyocytes and gene expression profiles of EMBs were analyzed. DCM patients displaying improvement of LVEF (≥ 20% relative and ≥ 5% absolute) six month after IA/IgG were considered responders. Compared to non-responders (n=16), responders (n=24) displayed shorter disease duration (p=0.006), smaller LV internal diameter in diastole (LVIDd) (p=0.019) and stronger NIA of antibodies. Antibodies obtained from controls were devoid of NIA. Myocardial gene expression patterns were different in responders and non-responders for genes of oxidative phosphorylation, mitochondrial dysfunction, hypertrophy, and ubiquitin proteasome pathway. Integration of scores of NIA and expression levels of four genes allowed robust discrimination of responders from non-responders at baseline (sensitivity of 100 % (95% CI, 85.8%-100%); specificity up to 100% (95 % CI, 79.4%-100%, cut-off value: -0.28), and was superior to scores derived from antibodies, gene expression or clinical parameters only. Conclusion: Combined assessment of NIA of antibodies and gene expression patterns of DCM patients at baseline predicts response to IA/IgG therapy and may enable appropriate selection of patients who benefit from this therapeutic intervention.
2012-12-01 | GSE17800 | GEO
Project description:Despite the increasing of available drugs in RA, the overall rate of non response is 30 to 40% of treated patients. To optimize the drug prescription and better elaborate the therapeutic strategies, gene profiling in PBMCs was used to predict the responsiveness to anakinra. Thirty two patients treated by anakinra (100mg/day s.c.) and méthotrexate, were categorized as responders whenever a change of Disease Activity Score 28 > 1.2 was obtained at 3 months. Blood from treated patients was collected at baseline. In 7 responders and 7 non responders, 51 mRNAs identified by microarray were expressed as a function of the response to treatment and an unsupervised hierarchical clustering perfectly separated responders from non responders. Keywords: anakinra effect PBMC then RNA were extracted from blood samples of 7 anakinra responders, 7 anakinra non responders and 1 pool of healthy subjects used as control. Each sample was hybridized twice in different nylon membrane. The control sample was hybridized twice in each nylon membrane.
2010-06-26 | E-GEOD-11827 | biostudies-arrayexpress
Project description:Fingolimod is an immunomodulatory sphingosine-1-phosphate (S1P) analogue approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). The identification of biomarkers of clinical response to fingolimod is a major necessity in MS to identify optimal responders and avoid the risk of disease progression in non-responders. With this aim, we used RNA-sequencing to study the transcriptomic changes induced by fingolimod in peripheral blood mononuclear cells of MS-treated patients and their association with clinical response. Samples were obtained from 10 RRMS patients (5 responders and 5 non-responders) at baseline and at 12 months of fingolimod therapy. Fingolimod exerted a vast impact at the transcriptional level, identifying 7155 differentially expressed genes (DEGs) compared to baseline that affected the regulation of numerous signalling pathways and cellular processes. These DEGs were predominantly immune-related, including genes associated with S1P metabolism, cytokines, lymphocyte trafficking, master transcription factors of lymphocyte functions and the NF-kB pathway. Responder and non-responder patients exhibited a differential transcriptomic regulation during fingolimod treatment, with responders presenting a higher number of DEGs (6405) compared to non-responders (2653). These transcriptomic differences offer the potential of being exploited as biomarkers of clinical response to fingolimod.
2024-01-31 | GSE250453 | GEO
Project description:Myelodysplastic syndromes and chronic myelomonocytic leukemia (CMML) are characterized by mutations in epigenetic modifiers and aberrant DNA methylation. DNA methyltransferase inhibitors (DMTis) are used to treat these disorders, but response is highly variable with few means to predict which patients will benefit. To develop a molecular means of predicting response at diagnosis, we examined baseline differences in mutations, DNA methylation, and gene expression in 40 CMML patients responsive and resistant to decitabine (DAC). While somatic mutations did not differentiate responders and non-responders, we were able to identify for the first time 158 differentially methylated regions (DMRs) at baseline between responders and non-responders using next-generation sequencing. These DMRs were primarily localized to non-promoter regions and overlapped with distal regulatory enhancers. Using the methylation profiles, we developed an epigenetic classifier that accurately predicted DAC response at the time of diagnosis. We also found 53 differentially expressed genes between responders and non-responders. Genes up-regulated in responders were enriched in the cell cycle, potentially contributing to effective DAC incorporation. Two chemokines overexpressed in non-responders -- CXCL4 and CXCL7 -- were able to block the effect of DAC on normal CD34+ and primary CMML cells in vitro, suggesting their up-regulation contributes to primary DAC resistance. mRNA profiling in bone marrow mononuclear cells (BM MNC) from 14 CMML patients (8 decitabine responders vs. 6 non-responders).
2015-03-31 | E-GEOD-61162 | biostudies-arrayexpress
Project description:Myelodysplastic syndromes and chronic myelomonocytic leukemia (CMML) are characterized by mutations in epigenetic modifiers and aberrant DNA methylation. DNA methyltransferase inhibitors (DMTis) are used to treat these disorders, but response is highly variable with few means to predict which patients will benefit. To develop a molecular means of predicting response at diagnosis, we examined baseline differences in mutations, DNA methylation, and gene expression in 40 CMML patients responsive and resistant to decitabine (DAC). While somatic mutations did not differentiate responders and non-responders, we were able to identify for the first time 158 differentially methylated regions (DMRs) at baseline between responders and non-responders using next-generation sequencing. These DMRs were primarily localized to non-promoter regions and overlapped with distal regulatory enhancers. Using the methylation profiles, we developed an epigenetic classifier that accurately predicted DAC response at the time of diagnosis. We also found 53 differentially expressed genes between responders and non-responders. Genes up-regulated in responders were enriched in the cell cycle, potentially contributing to effective DAC incorporation. Two chemokines overexpressed in non-responders -- CXCL4 and CXCL7 -- were able to block the effect of DAC on normal CD34+ and primary CMML cells in vitro, suggesting their up-regulation contributes to primary DAC resistance. DNA methylation profiling in bone marrow mononuclear cells (BM MNC) from 39 CMML patients (19 decitabine responders vs. 20 non-responders).
2015-03-31 | E-GEOD-61161 | biostudies-arrayexpress
Project description:Bronchial thermoplasty (BT) is an endoscopic therapy employed for the treatment of refractory asthma. However, no predictive factors are available that determine the effectiveness of BT in treating asthma patients. The present study aimed to comprehensively analyze RNA samples from the airway bronchial tissues of 8 patients with severe asthma treated by BT, and to characterize each patient as a BT responder or non-responder. Total 24 RNA samples (three per patient prior to BT1 [baseline], prior to BT2 [after 1st time treatment], and prior to BT3 [after 2nd time treatment]) were obtained. There were 975 differentially expressed (DE) genes in the bronchial tissues of 8 patients between prior to BT1 (baseline) and prior to BT2 (after 1st time treatment), with significant differences (FDR-adjusted P<0.05). Subjects with an Asthma Quality of Life Questionnaire score change of >0.5 for a period of 12 months were considered BT responders. Non-responders exhibited a score change of <0.5 for 12 months. Transcriptome analysis at baseline identified 67 genes that were differentially expressed between responders and non-responders, including SLPI, MMP3, and MUC19 which were upregulated in responders.
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