Mechanism of DYRK1A in Cytarabine Resistance in Acute Myeloid Leukemia.
10.19746/j.cnki.issn.1009-2137.2025.03.004
- Author:
Jia-Wei FENG
1
;
Hong-Juan YU
1
Author Information
1. Department of Hematology, Southern University of Science and Technology Hospital, Shenzhen 518055, Guangdong Province, China.
- Publication Type:Journal Article
- Keywords:
acute myeloid leukemia;
dual-specificity tyrosine phosphorylation-regulated kinase 1A;
cytarabine resistance;
cyclin L2;
sterile alpha motif and histidine/aspartic acid domain containing protein 1
- MeSH:
Humans;
Cytarabine/pharmacology*;
Protein-Tyrosine Kinases/metabolism*;
Leukemia, Myeloid, Acute;
Dyrk Kinases;
Drug Resistance, Neoplasm;
Protein Serine-Threonine Kinases/metabolism*;
SAM Domain and HD Domain-Containing Protein 1;
Cell Line, Tumor
- From:
Journal of Experimental Hematology
2025;33(3):648-652
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the role of DYRK1A in the cytarabine (Ara-C) resistance mechanism of acute myeloid leukemia (AML) cells.
METHODS:Overexpression and silencing of DYRK1A gene in THP-1 cells were used to observe whether the sensitivity of THP-1 cells to Ara-C was altered. RT-PCR was used to detect the changes in mRNA expression of related genes during Ara-C transport or metabolism. Western blot and RT-PCR were used to detect SAMHD1 expression after regulating DYRK1A expression in Ara-C treated cells. Co-IP technology was used to detect the interaction between Cyclin L2, DYRK1A, and SAMHD1.
RESULTS:Overexpression of DYRK1A decreased Ara-C sensitivity in THP-1 cells while silencing DYRK1A increased it. Overexpression and silencing of DYRK1A did not affect Ara-C transport or metabolic gene expression. Overexpression of DYRK1A could increase the expression of SAMHD1 protein in cells, while silencing DYRK1A reduced SAMHD1 expression. Cyclin L2 interacted with DYRK1A and SAMHD1 in THP-1 cells.
CONCLUSION:DYRK1A is involved in Ara-C resistance in AML cells, and its mechanism may be related to increased expression of SAMHD1 by interacting with Cyclin L2.
