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Status |
Public on Jun 08, 2023 |
Title |
Effects of fucosylation inhibitors on ATRA differentiation in myeloid leukemia cells |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
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, FcRI, 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.
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Overall design |
We use 4 samples. As a control, we used DMSO sample. The other samples are ATRA, 6AF and ATRA+6AF. All samples were exposed to reagents for 72 hours.
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Contributor(s) |
Suzuki S, Takahashi S |
Citation missing |
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Submission date |
Jun 05, 2023 |
Last update date |
Jun 10, 2023 |
Contact name |
Susumu Suzuki |
Organization name |
Tohoku Medical and Pharmaceutical University
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Street address |
1-15-1
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City |
Sendai-shi |
ZIP/Postal code |
983-8536 |
Country |
Japan |
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Platforms (1) |
GPL23159 |
[Clariom_S_Human] Affymetrix Clariom S Assay, Human (Includes Pico Assay) |
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Samples (4)
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Relations |
BioProject |
PRJNA980119 |
Supplementary file |
Size |
Download |
File type/resource |
GSE234103_RAW.tar |
4.4 Mb |
(http)(custom) |
TAR (of CEL) |
Processed data included within Sample table |
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