Effect of decitabine on gene expression in THP-1 or decitabine-resistant THP-1 leukemia cells
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PROVIDER: PRJNA1120476 | ENA |
REPOSITORIES: ENA
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Project description:To globally evaluate transcriptome in THP-1 and decitabine-resistant THP-1 cells treated by decitabine, cells were treated with the IC90 dose of decitabine until 90% cell death was reached, then cultured in decitabine-free medium until confluence, followed by another round of decitabine treatment and the treatment cycles were repeated for 3 months to generate decitabine-resistant THP-1 cells. We then performed gene expression profiling analysis using data obtained from RNA-seq of THP-1 or decitabine-resistant THP-1 cells treated with or without decitabine.
2025-06-28 | GSE269185 | GEO
Project description:Next Generation Sequencing Facilitates Quantitative Analysis of THP-1 cells treated with DMSO and Decitabine
2024-05-10 | GSE200510 | GEO
Project description:To explore the mechanisim and signaling pathway of hypomethylating agent decitabine in reversing P-glycoprotein(P-gp) induced multidrug resistance, we used adriamycin to treat drug sensitive human chronic myeloid leukemia K562 cells(KS) and successfully induced multidrug-resistant K562/ADR (KA) cells that higher expression of drug efflux pump P-gp. Gene expression profile was used to analysis the difference gene expression before and after treated with decitabine in both KS and KA cells.
2018-03-01 | GSE93942 | GEO
Project description:We found previously that the effect of decitabine (DAC) on hematopoietic stem cell viability differed between Mll5 wildtype and null cells. We therefore investigated the role of MLL5 expression levels on outcome of AML patients who were treated with decitabine. High MLL5 expressing AML patients have improved overall survival when treated with decitabine. In transformed murine cells, loss of Mll5 was associated with resistance to low-dose decitabine, less frequent promoter methylation, and reduced demethylation upon decitabine treatment. These data suggest a biological link between MLL5 expression and decitabine response involving regulation of DNA methylation. Leukemia cell model was generated by co-transfer of HOXA9 and MEIS1 into Mll5 wildtype or knockout mouse bone marrow cells. MeDIP was performed in Mll5+/+ HOXA9/MEIS1 and Mll5-/- HOXA9/MEIS1 leukemic cells, untreated or treated with 3-day exposure of 20 nM decitabine, triplicate for each condition. MeDIP-enriched DNA was amplified with the GenomePlex Complete Whole Genome Amplification (WGA) Kit (Sigma-Aldrich). DNA from three MeDIP and WGA of each cell type and treatment was pooled for subsequent microarray analysis. The enriched DNA and corresponding input genomic DNA was labeled, hybridized and scanned on Agilent custom mouse promoter microarrays (Agilent-025976 AP_1M_Custom_CH3, assembly build mm9). The methylation value of individual probes was defined by the signal intensity ratio of MeDIP DNA (Cy3) compared to input DNA (Cy5) . Methylated DNA immunoprecipitation coupled with Agilent mouse promoter CpG arrays (MeDIP-chip)
2014-07-01 | E-GEOD-52199 | biostudies-arrayexpress
Project description:Purpose: We aimed to investigate the effect of several anti-leukemia drugs in combination with decitabine (DAC) on the proliferation of myeloid leukemia cells in vitro and in vivo, to select the most efficient combination group and explore associated mechanisms of these combination therapies. Experimental Design: After comparing with five anti-leukemia drugs in several different kinds of cell lines, the combination effect of idarubicin (IDA) with DAC was best. In vivo, by using microPET, TUNEL, and transmission electron microscopy, the inhibitory effects obtained by sequentially combining DAC with IDA, evidenced by evaluating tumor cell proliferation and cell apoptosis. Molecular studies were conducted using gene chip, which was used to explore associated pathways, and real-time quantitative reverse transcription-PCR, western blot and immunohistochemistry (IHC), used to assess regulation of Wnt/β-catenin pathway. Results: The sequential combination of DAC and IDA showed synergistic induction of cell death in U937, HEL, SKM-1 and cells isolated from AML patients. Importantly, the inhibition of tumor growth in the sequential combination group was found to be significantly higher than that of single drug group or control group in vivo. Moreover, sequential treatment with DAC and IDA induced apoptosis and depression of the Wnt/β-catenin pathway in both culture and animal studies. Conclusions: Our findings showed that sequentially combining decitabine with idarubicin had a synergistic anti-leukemia effect. These findings were attributed to demethylation of Wnt pathway inhibitors and downregulation of Wnt pathway nuclear targets observed in vitro and in vivo. After comparing with five anti-leukemia drugs in several different kinds of cell lines, the combination effect of idarubicin (IDA) with DAC was best. In vivo, by using microPET, TUNEL, and transmission electron microscopy, the inhibitory effects obtained by sequentially combining DAC with IDA, evidenced by evaluating tumor cell proliferation and cell apoptosis. Molecular studies were conducted using gene chip, which was used to explore associated pathways, and real-time quantitative reverse transcription-PCR, western blot and immunohistochemistry (IHC), used to assess regulation of Wnt/β-catenin pathway.
2014-02-13 | E-GEOD-54918 | biostudies-arrayexpress
Project description:Decitabine induces the expression of genes in THP-1 cells
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Project description:Generated AZA resistant cell line (TAR) and analysis markedly different gene expression levels between THP-1 and TAR. Two condition experiment, THP-1 control vs. AZA resistant cell line.
2012-04-27 | E-GEOD-37630 | 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
Project description:We found previously that the effect of decitabine (DAC) on hematopoietic stem cell viability differed between Mll5 wildtype and null cells. We therefore investigated the role of MLL5 expression levels on outcome of AML patients who were treated with decitabine. High MLL5 expressing AML patients have improved overall survival when treated with decitabine. In transformed murine cells, loss of Mll5 was associated with resistance to low-dose decitabine, less frequent promoter methylation, and reduced demethylation upon decitabine treatment. These data suggest a biological link between MLL5 expression and decitabine response involving regulation of DNA methylation. Leukemia cell model was generated by co-transfer of HOXA9 and MEIS1 into Mll5 wildtype or knockout mouse bone marrow cells. MeDIP was performed in Mll5+/+ HOXA9/MEIS1 and Mll5-/- HOXA9/MEIS1 leukemic cells, untreated or treated with 3-day exposure of 20 nM decitabine, triplicate for each condition. MeDIP-enriched DNA was amplified with the GenomePlex Complete Whole Genome Amplification (WGA) Kit (Sigma-Aldrich). DNA from three MeDIP and WGA of each cell type and treatment was pooled for subsequent microarray analysis. The enriched DNA and corresponding input genomic DNA was labeled, hybridized and scanned on Agilent custom mouse promoter microarrays (Agilent-025976 AP_1M_Custom_CH3, assembly build mm9). The methylation value of individual probes was defined by the signal intensity ratio of MeDIP DNA (Cy3) compared to input DNA (Cy5) .
2014-07-01 | GSE52199 | GEO
Project description:Purpose: We aimed to investigate the effect of several anti-leukemia drugs in combination with decitabine (DAC) on the proliferation of myeloid leukemia cells in vitro and in vivo, to select the most efficient combination group and explore associated mechanisms of these combination therapies. Experimental Design: After comparing with five anti-leukemia drugs in several different kinds of cell lines, the combination effect of idarubicin (IDA) with DAC was best. In vivo, by using microPET, TUNEL, and transmission electron microscopy, the inhibitory effects obtained by sequentially combining DAC with IDA, evidenced by evaluating tumor cell proliferation and cell apoptosis. Molecular studies were conducted using gene chip, which was used to explore associated pathways, and real-time quantitative reverse transcription-PCR, western blot and immunohistochemistry (IHC), used to assess regulation of Wnt/β-catenin pathway. Results: The sequential combination of DAC and IDA showed synergistic induction of cell death in U937, HEL, SKM-1 and cells isolated from AML patients. Importantly, the inhibition of tumor growth in the sequential combination group was found to be significantly higher than that of single drug group or control group in vivo. Moreover, sequential treatment with DAC and IDA induced apoptosis and depression of the Wnt/β-catenin pathway in both culture and animal studies. Conclusions: Our findings showed that sequentially combining decitabine with idarubicin had a synergistic anti-leukemia effect. These findings were attributed to demethylation of Wnt pathway inhibitors and downregulation of Wnt pathway nuclear targets observed in vitro and in vivo.
2014-02-13 | GSE54918 | GEO