关键词: 儿童急性髓系白血病, 柔红霉素, 耐药, 程序性死亡受体配体-1

Abstract: Objective To explore the correlation between daunorubicin (DNR) resistance and expression of programmed 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 Hospital 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 lentiviral vectors were constructed. The effect and mechanism of PD-L1 on DNR resistance in Molm-13 cells were analyzed. 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 dehydrogenase (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 regulation of G6PD.

Key words: acute myeloid leukemia in children, daunorubicin, drug resistance, programmed death receptor ligand-1