Effect of Decitabine on SKM-1 and MDS-L Gene Expression
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PROVIDER: PRJNA691877 | ENA |
REPOSITORIES: ENA
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Project description:In order to further study the mechanism of decitabine (DAC) on MDS cell lines, 1uM DAC was used to treat SKM-1 and MDS-L cell lines, and the molecular pathway changes regulated by DAC were explored. Genes whose expression changes more than 2.0 times after drug treatment are defined as regulated genes. Taking the intersection change of the two cell lines, it was found that compared with the control, 541 genes were up-regulated in the intersection of gene changes treated with DAC, and 762 genes were down-regulated. Gene expression profile analysis shows that DAC can significantly affect various cell biological processes, including antiviral response, immune response, inflammatory response and cell apoptosis.
2021-01-26 | GSE164744 | GEO
Project description:Epigenetic mechanisms contribute to deregulated gene expression of hematopoietic progenitors in Myelodysplastic Syndromes (MDS). Hypomethylating agents are able to improve peripheral cytopenias in MDS patients. To identify critical gene expression changes induced by hypomethylating agents, we analyzed gene expression profiling (GEP) of myelodysplastic and normal CD34+ hematopoietic stem cells treated in vitro with or without decitabine. Four MDS and two untreated early stage Hodgkin’s lymphomas were analyzed for GEP. Mock treated CD34+ stem cells segregate according to diagnosis and karyotype. After decitabine treatment, gene expression changes were more consistent on MDS CD34+ cells with abnormal kayotype. Comparing decitabine-induced genes with those found down-regulated in mock-treated MDS cells, we identified a list of candidate tumor suppressor genes in MDS. By real-time RT-PCR we confirmed expression changes for three selected genes CD9, CXCR4 and GATA2 in 12 MDS patients and 4 controls. CD9 was widely repressed in most MDS CD34+ cell samples, although similar levels of methylation were found in both normal and MDS total bone marrows. CXCR4 promoter methylation was absent in total bone marrows from 36 MDS patients. In conclusion, changes in gene expression changes induced by hypomethylating treatment are more pronounced in CD34+ cells from abnormal karyotype.
2009-12-23 | GSE19610 | GEO
Project description:Myelodysplastic syndromes (MDS) are a group of clonal myeloid neoplasms characterized by ineffective hematopoiesis and cytopenia. Hypomethylating agents (HMAs) play a central role in the treatment of high-risk MDS, but their mechanisms of action are diverse and not fully understood. To investigate the molecular mechanisms of HMA, an MDS cell line (MDS-L) was cultured with a non-toxic concentration of decitabine for 6 months and drug sensitivity, cell differentiation, and DNA methylation profiles were evaluated. Cells with long-term exposure to decitabine (MDS-L-DAC) were morphologically mature with nuclear lobulation and cytoplasmic granulation, accompanied by decreased expression of the CD34 surface antigen. MDS-L-DAC cells exhibited decreased WT1 expression and intense induction of apoptosis by DAC. DNA methylation array analysis revealed the demethylation of the membrane spanning 4-domains A3 (MS4A3) genes and microRNA-143 (MIR143) in MDS-L-DAC cells. MIR143 functions as a tumor suppressor through the MAPK/ERK pathway, and in MDS-L-DAC cells, decreased expression of KRAS and β-catenin was observed in response to the increased expression of MIR143. The differentiation of MDS cells and decreased expression of WT1 induced by long-term incubation with DAC may involve the restoration of function via demethylation of the MIR143 and MS4A3 gene promoters, which may contribute to eliminating the malignant phenotype through reductions in KRAS and β-catenin expression.
2025-04-06 | GSE293053 | GEO
Project description:Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) with complex and monosomy karyotype (CK/MK) show high prevalence of TP53 mutations, poor response to induction chemotherapy and adverse patient outcome. These diseases may respond to decitabine but the mechanisms are presently unclear. MDS/AML patients were treated with decitabine for 10 days in a Phase II clinical study. In this study, we collected serial samples from patients before and at completion of decitabine treatment, morphologic remission and relapse. The samples were interrogated with targeted myeloid panel sequencing, nanopore DNA cytosine methylation sequencing and single-cell transcriptomics to investigate potential interactions between leukemic and immune populations. The integrative analysis allowed characterization of shifting dynamics within leukemic and immune cell populations in individual patients. Comparison of these trends between TP53 mutated MDS/AML patients who responded to treatment versus TP53 wildtype patients who were refractory to treatment highlighted the complex interplay of leukemic and immune compartments. Single cell transcriptomic analyses confirmed immune activation in TP53m responders after decitabine treatment. At relapse, leukemic populations showed up-regulation of MYC signaling and heat shock response while T-cells showed exhaustion signature. Our work highlighted the complex interplay between leukemic and immune populations in TP53m patients upon decitabine treatment that might account for clinical responses and subsequent relapses.
2025-02-10 | GSE279925 | GEO
Project description:To evaluate the impact of DNA demethylating agents on our mouse MDS model, we chose 5-aza-2’-deoxycytidine, decitabine (DAC), one of the DNA demethylating agents, which is incorporated into DNA but not RNA and has 10-fold more potency in DNA demethylation than 5-azacitidine. We transplanted Tet2KD/KDEzh2Δ/Δ MDS cells into lethally irradiated secondary recipients and treated them with DAC (low dose DAC at 0.25mg/kg, 3 times a week, intraperitoneal injection), then purified LSK HSPCs and evaluated the expression profiles.
2017-03-15 | GSE79204 | GEO
Project description:SUM159 BrCa Decitabine Gene Expression
| PRJNA553252 | ENA
Project description:Global DNA methylation was analyzed in total bone marrow cells of AML/MDS patients undergoing decitabine treatment.
2016-04-30 | GSE80762 | GEO
Project description:Epigenetic changes play a role in the pathogenesis of myeloid malignancies and hypomethylating agents have shown efficacy in these diseases. We studied the apoptotic effect, the genome-wide methylation and gene expression profiles in HL60 cells following decitabine treatment, using micro-array technologies. Decitabine treatment resulted in a decrease in global DNA methylation, corresponding to 4876 probeset IDs with significantly reduced methylation levels, while expression of 2583 IDs was induced. The integrated analysis identified 160 genes demethylated and upregulated by decitabine, mainly including development and differentiation pathways genes. Genes target of polycomb group protein regulation were overrepresented in this group. Apoptosis was induced by decitabine and apoptosis-specific PCR arrays more precisely indicated decitabine-induced upregulation of 13 apoptosis-related genes, in particular Dap-kinase 1 and Bcl2L10. Correspondingly, in primary patient samples, BCL2L10 was hypermethylated in 45% of AML, 43% of therapy-related myeloid neoplasms, 12% of MDS and in none of the controls.
2010-09-21 | GSE24224 | GEO
Project description:To further investigate the action mechanisms of decitabine (DAC), the molecular pathways regulated by DAC were explored using the gene expression profile of MDS-L cells treated with 4 nM DAC or DMSO for 7 days. Genes whose expression changed by more than 2.0-fold following drug treatment were defined as regulated genes. 956 genes were up-regulated and 461 genes down-regulated in MDS-L cells treated with DAC (4 nM) as compared with the control. Gene expression profiling suggested that DAC significantly affects various gene biogroups, including cellular movement, inflammatory response, hematological system development and function, hematopoiesis, and cell death. Decitabine-induced gene expression in MDS-L cells was measured after 7 days exposure at dose of 4 nM. Three independent samples.
2012-09-01 | E-GEOD-39628 | biostudies-arrayexpress
Project description:The DNA hypomethylating drug decitabine maintains normal hematopoietic stem and progenitor cell (HSPC) self-renewal but induces terminal differentiation in acute myeloid leukemia (AML) cells. To better understand the basis for this contrasting treatment effect, the baseline expression of key lineage-specifying transcription factor (TF) (eg., CEBPa) and key late differentiation TF (CEBPe), was examined in normal, myelodysplastic (MDS) and AML primary cells and cell lines. To appreciate the role of differentiation in hypomethylation of some CpG by decitabine treatment but not others, promoter CpGs, analyzed by microarray and mass spectrometry, were categorized by the direction of methylation change during normal myeloid differentiation. In MDS/AML cells, high expression of CEBPa, relatively low expression of CEBPe (a gene target of CEBPa), hypermethylation of CEBPe promoter CpG, and the methylation pattern at differentiation sensitive promoter CpGs analyzed by microarray, suggested lineage-commitment and aberrant epigenetic repression of late differentiation genes. DNA hypomethylation in response to decitabine was greatest at CpGs that are hypomethylated during normal myeloid differentiation. In contrast, normal HSPC treated with decitabine retained immature morphology, and methylation significantly decreased at CpG that are hypermethylated during myeloid differentiation. Partial differentiation at baseline, and repression of key late differentiation genes by epigenetic means, likely plays a role in methylation and phenotype responses of AML cells treated with decitabine. Bisulphite converted DNA from the 208 samples were hybridised to the Illumina Cancel Panel 1 GPL9183 methylation assay
2011-07-01 | E-GEOD-29047 | biostudies-arrayexpress