Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Effects of fucosylation inhibitors on ATRA differentiation in myeloid leukemia cells

ABSTRACT: Differentiation therapy with all-trans retinoic acid (ATRA) is well established for acute promyelocytic leukemia (APL). However, the narrow application and tolerance development of ATRA remain to be improved. In this study, we challenged glycosylation inhibitor to obtain better efficiency than ATRA alone. As a result, we found that the combination of fucosylation inhibitor 6-alkynylfucose (6AF) with ATRA have profound effect for differentiation, shown by expression changes of differentiation markers CD11b, CD11c, with significant morphological change in NB4 and HL-60 cells. From lectin blot assay, we found that ATRA or 6AF alone could decrease core fucosylation, the combination of these two agents efficiently decreases the expression of core fucosylation. To reveal molecular mechanisms to reveal 6AF effect for ATRA induced differentiation, we next performed microarray analysis using NB4 cells. From pathway analysis using DAVID software, we found that C-type lectin receptor (CLR) signaling pathway was enriched as high significance. From real time PCR analysis, using NB4 and HL-60 cells, FcRI, CLEC6A, CASP1, IL-1, EGR2/3, the components of CLR, and Akt, were indeed upregulated by 6AF in ATRA induced differentiation. These suggest that the involvement of CLR signaling pathway in 6AF effect of ATRA induced differentiation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE234103 | GEO | 2023/06/08

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Proteome dynamics of HL-60, NB4, and K562 cells under the ATRA treatment

Project description:Searching for new strategies of acute myeloid leukemia (AML) treatment is of particular interest. Cell lines, e. g. HL-60 and NB4, represent model systems to study molecular features of leukemic cells. The all-trans-retinoic acid (ATRA) has proven itself to be an effective treatment for one of AML subtypes, i.e., acute promyelocytic leukemia (APL). At the same time, ATRA causes granulocytic differentiation of non-APL leukemic cells in vitro. Combination of new therapeutics with ATRA could improve efficiency of treatment. Studying the proteome perturbation in leukemic cells under the ATRA treatment allows to determine potential regulatory molecules that could be affected pharmacologically. Thus, the TMT-based proteomic profiles of HL-60, NB4, and K562 cell lines under the ATRA treatment were obtained at 0, 3, 12, 24, and 72 h after the ATRA treatment.

2024-06-23 | PXD050317 | Pride

Human HL-60 Cells: all-trans retinoic acid (ATRA) vs. ATRA plus arsenic trioxide (ATO)

Project description:Transcriptional profiling of human leukemia　HL-60 cells comparing ATRA treated HL-60 cells with ATRA plus ATO. Goal was to determine the effects of ATO on ATRA induced differentiation of HL-60 cells.

2015-03-31 | GSE67420 | GEO

Human HL-60 Cells: all-trans retinoic acid (ATRA) vs. ATRA plus arsenic trioxide (ATO)

Project description:Transcriptional profiling of human leukemia?HL-60 cells comparing ATRA treated HL-60 cells with ATRA plus ATO. Goal was to determine the effects of ATO on ATRA induced differentiation of HL-60 cells. Two-condition experiment, ATRA vs. ATRA plus ATO treated HL-60 cells.

2015-03-31 | E-GEOD-67420 | biostudies-arrayexpress

Acute myeloid leukemia cell line RNA-Seq

Project description:We performed RNA-Seq on acute promyelocytic leukemia (APL) cells treated with both all-trans retinoic acid (ATRA) and trichostatin A (TSA) to identify transcriptional changes potentially associated with changes in APL cell mechanical properties. As a control, we performed the same treatments and RNA-Seq analysis on HL-60 cells, which were derived from a patient diagnosed with APL but whose cells lacked the hallmark fusion gene associated with APL. We performed RNA-Seq on these three cell lines (AP-1060, NB4, HL-60) under different conditions (untreated, TSA, ATRA, TSA + ATRA), and identified differentially expressed genes between samples and conditions. This study identified differentially expressed genes and enriched gene sets associated with (1) a resistance to differentiation induced by ATRA or (2) changes in mechanical properties. Overall, we find evidence that ATRA resistance and mechanical properties may be linked by the degree of chromatin condensation in APL cells.

2021-05-26 | GSE175507 | GEO

Shotgun mass-spectrometry of HL-60 cell proteins for spectrum library development

Project description:ATRA-induced differentiation of HL-60 cells was studied using targeted mass-spectrometry including selected reaction monitoring (SRM) and parallel reaction monitoring (PRM) approach. PRM experiment was performed in time-course manner, without peptide standards usage. PRM data was inspected in Skyline 3.1 software. In order to check peptide identity we developed spectrum library based on shotgun mass-spectrometry data, which has been obtained for HL-60 cells protein samples at 0, 3, 24, 48 and 96h after ATRA treatment.

2017-11-09 | PXD006421 | Pride

Widespread multi-targeted therapy resistance via drug-induced secretome fucosylation

Project description:Cancer secretome is a reservoir for aberrant glycosylation. How therapies alter this post59 translational cancer hallmark and the consequences thereof remain elusive. Here we show that an elevated secretome fucosylation is a pan-cancer signature of both response and resistance to multiple targeted therapies. Large-scale pharmacogenomics revealed that fucosylation genes display widespread association with resistance to these therapies. In both cancer cell cultures and patients, targeted kinase inhibitors distinctively induced core fucosylation of secreted proteins less than 60 kDa. Label-free proteomics of N-glycomes revealed that fucosylation of the antioxidant PON1 is a critical component of the therapy66 induced secretome. Core fucosylation in the Golgi impacts PON1 stability and folding prior to secretion, promoting a more degradation-resistant PON1. Non-specific and PON1-specific secretome deglycosylation both limited the expansion of resistant clones in a tumor regression model. Our findings demonstrate that core fucosylation is a common modification indirectly induced by targeted therapies that paradoxically promotes resistance.

2023-04-05 | GSE160205 | GEO

Expression profiling of myeloid leukemia cell treated with vibsanine A, PMA and ATRA

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

Gene Expression-Based High Throughput Screening: HL-60 Cells Treated with ATRA and PMA

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 data set contains HL-60 cells treated in a time course, in replicate, with 1 uM all trans retinoic acid (ATRA) and 10 nM phorbol 12-myristate 13-acetate (PMA). Also included are untreated HL-60 controls. This data set was used to select marker genes that distinguish the undifferentiated from the PMA or ATRA differentiated states. Keywords = AML Keywords = leukemia Keywords = HL-60 Keywords = chemical genomics Keywords: repeat sample

2004-01-30 | GSE985 | GEO

RNF8 is responsible for ATRA resistance in variant acute promyelocytic leukemia with GTF2I/RARA fusion and the inhibition of the ubiquitin-proteasome pathway contributes to the reversion of ATRA resistance

Project description:GTF2I-RARA is a newly identified RARA fusion gene in variant acute promyelocytic leukemia (APL) with t(7;17)(q11;q21). Clinical manifestation in the patient showed that it is a sort of ATRA-insensitive oncogene and is different from the classic PML-RARA in terms of therapeutic reaction. To reveal the functional characteristics and regulating mechanism of the GTF2I-RARA fusion gene, we established a GTF2I-RARA-transfected HL-60 cell model and confirmed its resistance to ATRA. Compared with PML-RARA, GTF2I-RARA has a higher affinity to HDAC3 under the treatment of ATRA. Using the ChIP-sequencing approach, we identified 221 GTF2I-RARA binding sites in model cells, and found that the RING finger protein 8(RNF8) is a target gene of GTF2I-RARA, which participated in the disease progression and therapy resistance in APL with GTF2I-RARA transcript. The elevated RNF8 expression promotes the interaction between RARA and RNF8 and induced RARA ubiquitylation and degradation, resulting in attenuated transcriptional activation of RARA. Our results suggested that RNF8 is a key GTF2I-RARA downstream event. Using the combination of MG132 and ATRA to treat the GTF2I-RARA-HL-60 cells, a synergistic effect leading to GTF2I-RARA-HL-60 cell differentiation was confirmed. Taken together, the targeting of RNF8 may be an alternative choice for treatment in variant APL with GTF2I-RARA fusion.

2018-11-10 | GSE122354 | GEO

RNA seq of HL-60 cells in untreated, ATRA (All- trans retinoic acid) and Vitamin D3 treated conditions

Project description:The leukemic cell line HL-60 is widely used to study normal and aberrant myelopoiesis. HL-60 cells can be treated with ATRA (all-trans retinoic acid) and Vit-D3 (1,25-Dihydroxyvitamin D3, calcitriol) to differentiate into granulocytes and monocytes respectively. Induced myeloid differentiation helps us to understand the molecular basis of myeloid differentiation. To understand the genome-wide gene expression changes associated with HL-60 cells upon myeloid differentiation, RNA-sequencing was carried out. We subjected the HL-60 cells with 10 µM ATRA and 50 nM Vit-D3 for 72 hours. Post induction, the uninduced and induced cells were sorted based on CD11b and CD14 markers. The uninduced cells were negative for both the markers while ATRA and Vit D3 inductions were highly positive for CD11b-FITC and CD14-APC-H7 markers respectively. Two biological replicates were used for this experiment. Sorted cells were collected for RNA extraction using RNAeasy Kit from Qiagen and RNA quality was assessed using Bioanalyzer. High quality RNA with RIN values greater than 8, were used to generate library using TrueSeq stranded library preparation kit from Illumina following manufacturer’s instructions. Finally, barcoded libraries were pooled, and a final concentration of 10 nM was loaded in HiSeq 2500 Illumina platform and paired-end sequencing for 2*126 cycles were carried out.

2023-01-25 | E-MTAB-12267 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data