Association between daunorubicin resistance and PD-L1 protein expression in children with acute myeloid leukemia
10.16352/j.issn.1001-6325.2024.06.0833
- VernacularTitle:急性髓系白血病患儿柔红霉素耐药与PD-L1蛋白表达相关
- Author:
Lili SONG
1
;
Yujie GUAN
;
Ping MA
;
Ning LI
Author Information
1. 郑州大学附属儿童医院 血液肿瘤科,河南 郑州 450000
- Keywords:
acute myeloid leukemia in children;
daunorubicin;
drug resistance;
programmed death receptor ligand-1
- From:
Basic & Clinical Medicine
2024;44(6):833-839
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the correlation between daunorubicin(DNR)resistance and expression of pro-grammed death receptor ligand 1(PD-L1)in children with acute myeloid leukemia(AML).Methods Totally 110 bone marrow samples were selected from AML patients admitted to Zhengzhou University Affiliated Children's Hos-pital from January 2016 to December 2022 as the study group,50 bone marrow samples from normal bone marrow donors were used as the control group.Human AML cell lines HL60,THP-1,U-937,and Molm-13 were cultured,and the expression of PD-L1 protein was detected by Western blot.LV-PD-L1-shRNA and LV-PD-L1-WT-OE lenti-viral vectors were constructed.The effect and mechanism of PD-L1 on DNR resistance in Molm-13 cells were ana-lyzed.Results The expression level of PD-L1 protein was higher than that in control group and the expression level of PD-L1 protein in AMI cell lines was higher than that in healthy bone marrow mononuclear cells(BMMC)(P＜0.05).PD-L1 expression was related to white blood cell count,bone marrow primitive cell ratio,prognostic risk stratification and disease remission after two standard chemotherapy regimens in AML patients(P＜0.05).The overall survival rate of the PD-L1 high expression group was lower than that of the PD-L1 low expression group(P＜0.05).Compared with the LV-PD-L1-WT-OE group,the LV-PD-L1-shRNA group showed a decrease in PD-L1 mRNA expression,cell proliferation activity but an increased apoptosis rate(P＜0.05).LV-PD-L1-shRNA enhanced sensitivity of Molm-13 cells to DNR.TCGA database analysis showed that glucose 6-phosphate dehydro-genase(G6PD)was a potential target gene for PD-L1.Conclusions The high expression of PD-L1 in pediatric AML is related to chemotherapy resistance in children with AML,and DNR resistance might be caused through reg-ulation of G6PD.
