Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA192433 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The Affymetrix Human Genome U133 Plus 2.0 Array was used to examine the Genome wide transcriptional changes which follow the treatment of AML xenografts with either PBS control or combination of decitabine (DAC) and cytarabine (Ara-C). Animals were treated with PBS, DAC alone, Ara-C alone, DAC and Ara-C combined (D+A), DAC followed by Ara-C (D/A) or Ara-C followed by DAC (A/D). PBS vs each drug combination
2013-03-06 | E-GEOD-44857 | biostudies-arrayexpress
Project description:The Affymetrix Human Genome U133 Plus 2.0 Array was used to examine the Genome wide transcriptional changes which follow the treatment of AML xenografts with either PBS control or combination of decitabine (DAC) and cytarabine (Ara-C). Animals were treated with PBS, DAC alone, Ara-C alone, DAC and Ara-C combined (D+A), DAC followed by Ara-C (D/A) or Ara-C followed by DAC (A/D).
2013-03-06 | GSE44857 | GEO
Project description:Genome wide DNA methylation profiling of AML patient samples treated with PBS or DAC. The Illumina Infinium 450 Human DNA methylation was used to examine the methylation profile of 8 patient samples and 2 cell lines. Genome wide DNA methylation profiling of AML xenografts treated with either PBS control or with decitacine (DAC) alone, cytarabine (Ara-C) alone, DAC and Ara-C together (D+A), DAC followed by Ara-C (D/A) or with Ara-C followed by DAC (A/D).
2013-03-06 | GSE44830 | GEO
Project description:Genome wide DNA methylation profiling of AML patient samples treated with PBS or DAC. The Illumina Infinium 450 Human DNA methylation was used to examine the methylation profile of 8 patient samples and 2 cell lines. Genome wide DNA methylation profiling of AML xenografts treated with either PBS control or with decitacine (DAC) alone, cytarabine (Ara-C) alone, DAC and Ara-C together (D+A), DAC followed by Ara-C (D/A) or with Ara-C followed by DAC (A/D). DNA was extracted from patient bone marrow samples and xenograft bone marrow samples using Qiagen Allprep kit. Bisulphite converted DNA from all samples were hybridised to the Illumina Infinium 450 Human Methylation arrays and for each analysis the drug treated sample was compared to the corresponding PBS control sample.
2013-03-06 | E-GEOD-44830 | biostudies-arrayexpress
Project description:Acute myeloid leukemia (AML), and other myeloid malignancies, are frequently treated with hypomethylating agents like decitabine. Alterations in the epigenome, induced by decitabine, are likely to result in gene expression changes. The effects of decitabine have not been systemically studied using primary AML samples. We cultured 18 different primary AML samples for 7 days, the last 3 days of which included 100 nM decitabine (DAC) or 100 nm cytarabine (AraC). We hypothesized that decitabine treatment would result in detectable and consistent gene expression changes. For comparison, we also analyzed mRNA from cells treated with DMSO control (mock) and mRNA from uncultured cells taken at the time of diagnosis.
2012-12-18 | E-GEOD-40442 | biostudies-arrayexpress
Project description:Gene expression profiling in primary AML cells treated with decitabine and cytarabine
| PRJNA174047 | ENA
Project description:Genome-wide DNA methylation profiling of primary AML samples treated with 100nM decitabine (DAC), cytarabine (AraC), or DMSO. Eight distinct AML samples were grown using an in vitro stromal co-culture system for 4 days and then treated with either DAC, Ara-C or DMSO for 3 days. DNA was prepared for genome-wide methylation analysis with the Illumina Infinium 450k Human DNA methylation BeadChip. DNA from each sample/treatment was analyzed on duplicate arrays. Bisulfite-converted DNA from 24 samples was hybridised to the Illumina Infinium 450k Human Methylation Beadchip in duplicate (replicates are indicated by array plate number).
2012-12-18 | E-GEOD-40870 | biostudies-arrayexpress
Project description:Genome-wide DNA methylation profiling of primary AML samples treated with 100nM decitabine (DAC), cytarabine (AraC), or DMSO. Eight distinct AML samples were grown using an in vitro stromal co-culture system for 4 days and then treated with either DAC, Ara-C or DMSO for 3 days. DNA was prepared for genome-wide methylation analysis with the Illumina Infinium 450k Human DNA methylation BeadChip. DNA from each sample/treatment was analyzed on duplicate arrays.
2012-12-18 | GSE40870 | GEO
Project description:Patients with acute myeloid leukemia (AML) suffer dismal prognosis and the most adverse subpopulation within each tumor determines patient’s prognosis. To better understand challenging features in AML, we studied individual stem cells from a single AML sample, complementing genomic with in vivo functional studies. Primary tumor cells from an AML patient’s first and second relapse were transplanted into NSG mice to establish serially transplantable patient derived xenografts (PDX). In an innovative approach, twelve derivative PDX clones were generated thereof, each derived from a single AML stem cell as proven by molecular barcoding, and were color-marked to facilitate multiplex competitive in vivo assays. PDX clones consisted of four different genomic clusters; one cluster displayed resistance against Cytarabine treatment, while two other clusters harbored increased stem cell potential, indicating that stemness and treatment resistance had evolved independently in the sample. In vivo functional data correlated closely with the phylogenetic tree calculated from exome data. The Cytarabine-resistant cluster was characterized by a distinct gene expression profile, and a score thereof predicted outcome in large clinical patient data cohorts. Taken together, we provide proof of concept that intra-sample heterogeneity mimics inter-sample heterogeneity in AML. Stem cell disparities within a single sample allow insights into adverse characteristics of general importance for AML.
2022-04-04 | PXD026296 | Pride
Project description:Purpose: Decitabine is a deoxycytidine nucleoside derivative inhibitor of DNA-methyltransferases indicated for treatment of myelodysplastic syndrome (MDS). Laboratory evidence shows that pretreatment of AML cell lines can sensitize leukemia cells to chemotherapy and inhibit clonogenic potential. We conducted a randomized study of decitabine when used as priming before standard induction therapy in children with newly diagnosed acute myelogenous leukemia (AML) to evaluate the safety, pharmacokinetics, and any potential early efficacy signal. Exploratory analyses of genomic methylation and RNA expression patterns and minimal residual disease (MRD) were included to elucidate possible biological mechanisms. Methods: This multicenter, randomized, two-arm, open-label study enrolled children ages 1-16 with newly diagnosed de novo AML to either Arm A: daunorubicin, cytarabine, etoposide preceded by a 5-day course of decitabine (experimental arm) or Arm B: daunorubicin, cytarabine, etoposide (control). Following completion of induction therapy, subsequent post-induction treatment was given at the treating physician’s discretion. Patients were monitored for adverse events and samples were collected for PK/PD and biologic analyses. Results: Twenty patients, ages 1-16 years (median 9.4 yrs in both Arms) were treated (10 per Arm). Eighteen of 20 enrolled subjects completed the prescribed treatment. All subjects experienced neutropenia and thrombocytopenia as is expected during AML induction chemotherapy. The most common grade 3 and 4 non-hematologic adverse events observed were caecitis, 2 (20%) subjects in Arm A and 0 (0%) subjects in Arm B; decreased appetite, 3 (30%) subjects in Arm A and 0 (0%) subjects in Arm B; and hypophosphatemia, 2 (20%) subjects in Arm A and 0 (0%) subjects in arm B. One subject in Arm A had appendicitis and colon perforation on Day 6 that led to study discontinuation; the cause was later determined to have been leukemic infiltrate of the bowel wall. Two subjects died (both in Arm A), one of necrotic bowel, pseudomonas sepsis and multisystem organ failure 6 months after study participation and one patient 5 months following study treatment from multisystem organ failure as a complication of stem cell transplant. Plasma concentrations of decitabine showed PK values (mean+SD) of Cmax, 281+113 ng/mL, AUC0-∞, 198+65.3 ng*h/mL, CL, 156+94.6 L/h, Vdss 109+70 L, t1/2 0.48+0.060 h, and median tmax 0.93 h. Overall CR/CRi by morphology was similar between the two treatment arms (92% for the control arm and 100% for the experimental arm). MRD at Day 30 post induction therapy was lower in the control group compared to the decitabine group (67% vs 85% MRD-negative). Changes in DNA epigenetic and RNA expression patterns demonstrated distinct differences involving selective cellular pathways between the two groups of patients comparing diagnostic to day 30 bone marrow samples. Conclusions: This first-in-pediatric trial of epigenetic priming in patients with newly diagnosed AML demonstrates that decitabine pre-treatment followed by standard combination chemotherapy is well tolerated in children with newly diagnosed AML. Morphologic complete responses were similar in both treatment arms. MRD at Day 30 following induction therapy suggests a deeper remission in patients receiving decitabine. No differences were observed between treatment arms in hematologic toxicities although decitabine-treated patients were noted to have more gastrointestinal toxicities, anorexia and hypophosphatemia. Decitabine PK parameters in children were consistent with known adult PK profiles. Molecular changes associated with decitabine pretreatment may be important in the sensitization of clonogenic AML cells. Pre-treatment with decitabine may represent a therapeutic option for use in pediatric AML, when epigenetic modification is a desired focus for treatment.
2017-10-31 | GSE78963 | GEO