Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA119009 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:An increasing body of work reveals aberrant hypermethylation of genes occurring in and potentially contributing to the pathogenesis of myeloid malignancies. Several of these diseases, such as myelodysplastic syndromes (MDS), are responsive to DNA methyltransferase inhibitors. In order to determine the extent of promoter hypermethylation in such tumors we compared the distribution of DNA methylation of 14,000 promoters in MDS and secondary AML patients enrolled in a phase I trial of 5-azacytidine and the histone deacetylase inhibitor entinostat against de novo AML patients and normal CD34+ bone marrow cells. The MDS and secondary AML patients displayed more extensive aberrant DNA methylation involving thousands of genes than did the normal CD34+ bone marrow cells or de novo AML blasts. Aberrant methylation in MDS and secondary AML tended to affect particular chromosomal regions, occurred more frequently in Alu poor genes, and included prominent involvement of genes involved in the WNT and MAPK signaling pathways. DNA methylation was also measured at days 15 and 29 after the first treatment cycle. DNA methylation was reversed at day 15 in a uniform manner throughout the genome, and this effect persisted through day 29, even without continuous administration of the study drugs. Keywords: DNA methylation profiling Direct comparison of DNA methylation in bone marrow samples from patients with Myelodysplastic syndrome or secondary Acute Myeloid Leukemia (AML) at baseline and after in vivo treatment with 5-azacytidine + etinostat. A comparison to de novo normal karyotype AML was also performed. Two control groups were included: one consisting of 8 CD34+ bone marrow samples from healthy donors and a second one consisting of matched CD34+ and CD34- fractions from the bone marrows of 4 healthy donors.
2010-05-15 | E-GEOD-17328 | biostudies-arrayexpress
Project description:An increasing body of work reveals aberrant hypermethylation of genes occurring in and potentially contributing to the pathogenesis of myeloid malignancies. Several of these diseases, such as myelodysplastic syndromes (MDS), are responsive to DNA methyltransferase inhibitors. In order to determine the extent of promoter hypermethylation in such tumors we compared the distribution of DNA methylation of 14,000 promoters in MDS and secondary AML patients enrolled in a phase I trial of 5-azacytidine and the histone deacetylase inhibitor entinostat against de novo AML patients and normal CD34+ bone marrow cells. The MDS and secondary AML patients displayed more extensive aberrant DNA methylation involving thousands of genes than did the normal CD34+ bone marrow cells or de novo AML blasts. Aberrant methylation in MDS and secondary AML tended to affect particular chromosomal regions, occurred more frequently in Alu poor genes, and included prominent involvement of genes involved in the WNT and MAPK signaling pathways. DNA methylation was also measured at days 15 and 29 after the first treatment cycle. DNA methylation was reversed at day 15 in a uniform manner throughout the genome, and this effect persisted through day 29, even without continuous administration of the study drugs. Keywords: DNA methylation profiling
2009-08-05 | GSE17328 | GEO
Project description:Aplastic anaemia (AA) is a form of bone marrow failure (BMF) resulting in significant cytopenias and may progress with clonal evolution to myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). MicroRNA expression is dysregulated in MDS/AML but there are limited studies on its role in the pathogenesis of AA. Using stored BM samples (n=81) from 2006-2019 from 52 patients, we demonstrate key differences in miRNA expression between AA patients at diagnosis and de novo MDS patients (n=21). The five most significantly upregulated miRNA in MDS patients (downregulated in AA) were miR-130a-3p, miR-221-3p, miR-126-3p, miR-27b-3p and miR-196b-5p (adj p<0.001). However, at the time of AA clonal progression to secondary MDS/AML, no significant miRNA differences were identified suggesting that the underlying mechanistic pathways are similar between AA progression to MDS/AML and de novo MDS. At diagnosis, miR-127-3p, miR-1271-5p, miR-301b-5p, miR-3934-5p and miR-4531 (adj p=0.081) were upregulated in those whose AA eventually progressed in comparison to those without eventual clonal progression. Using KEGG pathway analysis derived from miRPathDBv2.0, cytokine-cytokine receptor interaction, TGF-, MAP kinase, prolactin, Hippo, neurotrophin and FOXO signalling pathways were enriched in AA patients with clonal progression to MDS/AML; these pathways were similarly enriched in the de novo MDS cohort. These studies highlight the differing miRNA expression profiles in AA and MDS and in AA clonal evolution to MDS/AML.
2023-09-02 | GSE242216 | GEO
Project description:AC133+ cells were prepared from bone marrow of individuals with acute myeloid leukemia (AML) with M2 subtype. Comparison was made between de novo AML and MDS-associated AML.
2003-10-09 | E-MEXP-25 | biostudies-arrayexpress
Project description:<p>We used massively parallel sequencing technology to sequence the genomic DNA of tumor cells (leukemic bone marrow) and normal cells (skin biopsy) obtained from patients with Acute Myeloid Leukemia (AML). Patients had either de novo AML (AML with no prior diagnosis of a hematologic disease or exposure to chemotherapy), secondary AML (occurring after a prior diagnosis of myelodysplastic syndromes (MDS)), or therapy-related AML (occurring after exposure to prior chemotherapy). We identified somatic mutations in the tumor genomes, including single nucleotide variants, insertions, deletions, and structural variants.</p>
| phs000159 | dbGaP
Project description:Peripheral blood samples of 3 refractory/relapsed AML patients (R/R-AML, relapsed/refractory AML patients who failed to achieve complete remission/CR after 2 courses of induction chemotherapy), 3 refractory secondary AML patients (S-AML, MDS or MPN derived AML patients did not reach CR after 2 rounds of induction chemotherapy), 4 de novo AML patients (AML, CR after standard “3+7” induction chemotherapy), and 3 healthy controls (HC) were collected. Nanodrop was applied to quantify the total RNA samples. Illumina kits were used to prepare the RNA-seq library.
2021-09-10 | GSE183817 | GEO
Project description:The MLL-PTD mutation is found in patients with MDS and AML, and not in other hematological malignancies. Previously, we showed that Mll-PTD knock-in heterozygous mice (MllPTD/WT mice) present with several MDS-associated features. However, these phenotypes are insufficient to constitute bona fide MDS. MllPTD/WT mice do not generate MDS or AML in primary or transplant recipient mice. This suggests that additional genetic and/or epigenetic defects are necessary for transformation to MDS or AML. In secondary AML and de novo AML, MLL-PTD mutation is significantly associated with mutations in RUNX1 and with the FLT3-ITD mutations. In fact, the combination of MLL-PTD with the FLT3-ITD allele leads to AML in mice. We combined the MLL-PTD with RUNX1 mutant proteins, in order to generate a new mouse model for MDS. We generated MllPTD/WT/Runx1Flox/Flox/Mx1-Cre mice to model loss-of-function RUNX1 mutations. To test the significance of HIF-1α in this model, we also generated MllPTD/WT/Runx1Flox/Flox/Hif-1αFlox/Flox/Mx1-Cre mice and genetically eliminated Hif-1α expression. We analyzed gene expression variations in the HSPCs comparing the MllPTD/WT/Runx1∆/∆ with or without HIF-1α abrogation.
2018-12-23 | GSE86953 | GEO
Project description:Genome wide DNA methylation profiling of normal and pathologic mesenchymal stromal cells (MSCs). The Illumina Infinium 850k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpGs total DNA from in vitro-amplified MSCs. Samples included 11 normal MSCs, 11 MSCs from MDS patients, and 10 MSCs from AML patients.
2021-12-11 | GSE124390 | GEO
Project description:Mutations in the RUNX1 gene (RUNX1mut) have been established in myelodysplasia (MDS), de novo and secondary acute myeloid leukaemia (AML), and are in general associated with an unfavourable clinical outcome. Familial RUNX1 mutations are associated with familial thrombocytopenia and these patients have a predisposition to AML development. However, a number of studies have been performed so far in mice which might be distinct from the human hematopoietic system. Therefore we studied the cellular phenotypes, the RUNX1 binding pattern and expression profile induced by RUNX1mut in cord blood (CB) CD34+ cells and induced pluripotent stem cell (iPSC) and compared these findings to primary RUNX1mut AML’s.
2019-02-06 | GSE111918 | GEO
Project description:Mutations in the RUNX1 gene (RUNX1mut) have been established in myelodysplasia (MDS), de novo and secondary acute myeloid leukaemia (AML), and are in general associated with an unfavourable clinical outcome. Familial RUNX1 mutations are associated with familial thrombocytopenia and these patients have a predisposition to AML development. However, a number of studies have been performed so far in mice which might be distinct from the human hematopoietic system. Therefore we studied the cellular phenotypes, the RUNX1 binding pattern and expression profile induced by RUNX1mut in cord blood (CB) CD34+ cells and induced pluripotent stem cell (iPSC) and compared these findings to primary RUNX1mut AML’s.
2019-02-06 | GSE111917 | GEO