Similar Datasets
Project description:m7G-MeRIP-sequencing for AML cells(HL-60) and drug-resistant AML Cells(HL60/MX2).
2022-04-23 | GSE201096 | GEO
Project description:RNA-Seq of human AML cell line, HL-60 and its mitoxantrone resistant subline HL60/MX2
| PRJEB37958 | ENA
Project description:N6-Methyladenosine (m6A) is the most abundant post-transcriptional modification in eukaryotes, the imbalance of which is reported to be associated with various pathological processes, including drug resistance. In this study, we analyzed the methylated RNA immunoprecipitation combined with next-generation sequencing (MeRIP-seq) data of AML cell line HL60 and its adriamycin-resistant cell line HL60/ADR. We found a total of 40550 peaks, representing 15640 genes in HL60, and a total of 38834 peaks, representing 15285 genes in HL60/ADR. A total of 4437 differentially methylated m6A peaks within 3461 genes have been found between HL60 and HL60/ADR. Among them, 3587 differentially m6A peaks within 2790 genes were hyper-methylated, and 850 m6A peaks within 671 genes were hypo-methylated. KEGG pathway analysis showed that pathways were enriched in tumor and drug-resistant related signaling pathway. Results of MeRIP-seq showed that fold enrichment of global m6A peaks was higher in HL60/ADR compared to HL60. This study provides a framework for the application of comprehensive mRNA m6A profiling towards acute myeloid leukemia cell line (HL60) and its adriamycin-resistant acute myeloid leukemia cell line (HL60/ADR).
2021-12-29 | GSE192618 | GEO
Project description:We developed a general approach to small molecule library screening called GE-HTS (Gene Expression-Based High Throughput Screening) in which a gene expression signature is used as a surrogate for cellular states and applied it to the identification of compounds inducing the differentiation of acute myeloid leukemia cells. In screening 1,739 compounds, we identified 8 that reliably induced the differentiation signature, and furthermore yielded functional evidence of bona fide differentiation. This SuperSeries is composed of the following subset Series:; GSE976: Gene Expression-Based High Throughput Screening: APL Treatment with Candidate Compounds; GSE982: Gene Expression-Based High Throughput Screening: HL-60 Cell Treatment with Candidate Compounds; GSE983: Gene Expression-Based High Throughput Screening: Primary Patient AML Blasts, Normal Neutrophils, and Normal Monocytes; GSE985: Gene Expression-Based High Throughput Screening: HL-60 Cells Treated with ATRA and PMA Experiment Overall Design: Refer to individual Series
2007-09-20 | E-GEOD-995 | biostudies-arrayexpress
Project description:Acute myeloid leukemia (AML) is a clonal hematopoietic malignancy, characterized by expansion of immature leukemic blasts in the bone marrow. In AML, specific tyrosine kinases have been implicated in leukemogenesis, and are associated with poor treatment outcome. However, targeted therapy using kinase inhibitors (KIs) has had limited success, and may be improved by proper patient selection. We performed phosphotyrosine (pY) based, label-free phosphoproteomics to identify hyperphosphorylated, active kinases in AML cell lines as targets and predictive biomarkers to select KIs for treatment. We identified 3605 class I phosphorylation sites in 16 AML cell lines (EOL-1, KG-1a, MM6, KG-1, ME-1, NB-4, Kasumi-3, MV4-11, THP-1, HEL, HL-60, Kasumi-1, Kasumi-6, ML-2, OCI-AML3, MOLM-13) that exhibited large variation in the number and level of phosphopeptides per cell line (241-2764). Ranking analyses successfully pinpointed the hyperactive kinases PDGFRA, FGFR1, KIT, and FLT3 in eight cell lines with a corresponding kinase mutation. Additionally, we identified unexpected drivers in two more cell lines (PDGFRA in Kasumi-3 and FLT3 in MM6) which proved sensitive to specific kinase inhibitors. Six cell lines without a clear receptor tyrosine kinase (RTK) driver showed evidence of MAPK1/3 activation, consistent with the presence of activating RAS mutations. Our data show the potential of pY phosphoproteomics to identify key drivers in AML cells, and the predictive value of the phosphoproteome profiles in TKi selection for targeted treatment.
2019-11-11 | PXD007237 | Pride
Project description:Background:Aberrant DNA methylation that silences tumor suppressor genes occurs frequently in patients with acute myeloid leukemia (AML). Treatment of AML patients with the inhibitor of DNA methylation, 5-aza-2'-deoxycytidine (5-AZA-CdR) can induce complete remissions, but most patients will relapse. The clinical efficacy of 5-AZA-CdR may be influenced by its limited capacity to activate tumor suppressor genes silenced by methylation of lysine 27 histone H3 (H3K27) by EZH2. In order to overcome this limitation, we investigated previously the antileukemic action of 5-AZA-CdR in combination with the EZH2 inhibitor, 3-deazaneplanocin A (DZNep) on HL-60 AML cells. We observed a remarkable synergistic interaction against these AML cells for this combination. In this study, we investigated in more depth the action of 5-AZA-CdR plus DZNep on gene expression in AML cells using RNA sequence analysis Result:In a colony assay, 5-AZA-CdR in combination with DZNep exhibited also a potent synergy against another human AML cell line: AML-3. The induction of apoptosis in HL-60 and AML3 leukemic cells by 5-AZA-CdR plus DZNep was also synergistic. RNA sequence analysis on HL-60 leukemic cells showed that the combination of 5-AZA-CdR plus DZNep increased the expression of thousands of genes. The genes upregulated by this combination included genes related to differentiation, development, senescence, apoptosis, and tumor suppressor function. Many of the genes activated by 5-AZA-CdR plus DZNep have the potential to suppress leukemogenesis. Conclusion: The activation of many genes by the combination of 5-AZA-CdR plus DZNep correlates with its synergistic antileukemic action. The block in differentiation is one of the hallmarks of AML.The activation of many genes that program differentiation and development by this combination of epigenetic agents has the potential to reverse this block. The reversal of these two epigenetic genesilencing mechanisms by 5-AZA-CdR plus DZNep merits clinical investigation in patients with AML
2017-02-01 | GSE94344 | GEO
Project description:To identify the mechanisms controlling chronic myeloid leukemia (CML) and acute myeloid leukemia (AML) in humans, we analyzed genome-wide transcription dynamics in three myeloid leukemia cell lines (K562, HL-60, and THP1) using high-throughput sequencing technology. Using KEGG analysis, we found that the ERK/MAPK, JAK-STAT and ErbB pathways promoted proliferation and metabolism in CML. However, in AML, differentiation and apoptosis blocking resulted in the accumulation of blast cells in marrow. In addition, each cell type had unique characteristics. K562 cells are an ideal model for studying erythroid differentiation and globin gene expression. The chemokine signaling pathway and Fc gamma R-mediated phagocytosis were markedly upregulated in HL-60 cells. In THP1 cells, highly expressed genes ensured strong phagocytosis by monocytes. Further, we provide a new insight into myeloid development. The abundant data sets and well-defined analysis methods will provide a resource and strategy for further investigation of myeloid leukemia. Compare mRNA transcriptomes of three different cell lines
2013-10-09 | E-GEOD-46164 | biostudies-arrayexpress
Project description:All-trans retinoic acid (ATRA)-based differentiation therapy has achieved success with the treatment of acute promyelocytic leukemia (APL), a unique subtype of acute myeloid leukemia (AML). However, other subtypes of AML display resistance to ATRA-based treatment. Here, we demonstrate that a novel natural vibsane-type diterpenoid vibsanine A promotes the differentiation of myeloid leukemia cell lines and primary AML blasts. To reveal how vibsanine A function on promoting myeloid leukemia cell differentiation, we analyzed and compared the gene expression profiles in myeloid leukemia HL-60 cells treated with vibsanine A, PMA, and ATRA. HL-60 cells were treated with vibsanine A, PMA and ATRA for 6 hours or longer up to 24 hours. Gene expression profiling was conducted
2016-02-28 | E-GEOD-78734 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-04-23 | GSE201097 | GEO
Project description:Alteration in metabolic repertoire is commonly associated with resistance phenotype. Although it’s a common phenotype, not much efforts have been undertaken to design effective strategies to target the metabolic drift in such cancerous cells and especially with drug resistant properties. In our study, we identified that drug resistant AML cell line HL-60/MX2 do not follow classical Warburg effect, instead these cells exhibit drastically low levels of aerobic glycolysis. Biochemical analysis confirms reduced glucose consumption and lactic acid production by resistant population with no differences in glutamine consumption. Raman spectroscopy revealed increased lipid and cytochrome content in resistant cells which were also visualized in the form of lipid droplets by Raman mapping, electron microscopy and lipid specific staining. Gene set enrichment analysis data from both the cell lines revealed significant enrichment of lipid metabolic pathways in HL-60/MX2 cells. Further drug resistant cells possess higher mitochondrial activity and increased OXPHOS suggested the role of fatty acid metabolism as energy source which was confirmed by increased rate of fatty acid oxidation. Pharmacological inhibition of fatty acid oxidation using Etomoxir affected the colony formation ability of resistant cells and inhibition of OXPHOS using Antimycin-A increased the sensitivity of resistant cells to chemotherapeutic drug, demonstrating requirement of fatty acid metabolism and increased dependency on OXPHOS by resistant leukemic cells for tumorigenicity.
2021-01-01 | E-MTAB-8981 | biostudies-arrayexpress