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中国生物工程杂志

China Biotechnology
China Biotechnology  2023, Vol. 43 Issue (12): 69-77    DOI: 10.13523/j.cb.2310055
    
The Expression of PD-L1 in Acute Myeloid Leukemia
DU Chen-xiao,PENG Lan,XIAO Xiang-yao,MA Jin-yu,TENG Guang-shuai,ZHANG Yu-hui,WANG Yan,DUAN Yi-fan,SHAO Zong-hong,BAI Jie()
Department of Hematology, the Second Hospital of Tianjin Medical University, Tianjin 300211, China
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Abstract  

Objective: To investigate the clinical significance of the expression level of programmed death molecule 1 ligand 1 (PD-L1) in the occurrence, transformation, and treatment of acute myeloid leukemia (AML). Methods: First, using GEO software and GEO2R calculation method, with P<0.05 and | logFC |>1 as conditions, we analyzed the expression of common immune monitoring points in public databases. The data were analyzed using TCGA-LAML queue data and survival R packets for high expression PD-L1 patients. Second, we selected newly diagnosed AML patients in our department from October 2017 to March 2023 to verify our hypothesis. Flow cytometry was used to detect the expression levels of PD-L1 in the bone marrow T lymphocyte programmed cell death receptor 1 (PD-1) and CD34+progenitor cells before treatment. The correlation between PD-1 and PD-L1 expression levels and patient clinical characteristics, efficacy, and survival was analyzed. Results: The expression of lymphocyte activation gene 3 (LAG3), PD-1, PD-L1, and T cell immunoglobulin domain and mucin domain-3 (TIM3) at immune checkpoint in the initially diagnosed AML patients was higher than that in normal individuals (P<0.05), and the survival rate was higher in the group with low PD-L1 expression at initial diagnosis. Recurrent and refractory AML and secondary AML have higher levels of PD-L1 expression at initial diagnosis. The high expression of PD-L1 in newly diagnosed AML patients tends to have complex chromosomal karyotypes, poorer prognosis, and shorter survival. Conclusions: The PD-1/PD-L1 signaling pathway may be involved in the immune escape mechanism of myeloid tumor cells, and its expression level is positively correlated with the malignancy and progression of the disease, while negatively correlated with treatment efficacy and survival.



Key wordsPD-L1      Myeloid tumors      Immune escape      Immunotherapy     
Received: 01 November 2023      Published: 16 January 2024
ZTFLH:  Q354  
Cite this article:

Chen-xiao DU, Lan PENG, Xiang-yao XIAO, Jin-yu MA, Guang-shuai TENG, Yu-hui ZHANG, Yan WANG, Yi-fan DUAN, Zong-hong SHAO, Jie BAI. The Expression of PD-L1 in Acute Myeloid Leukemia. China Biotechnology, 2023, 43(12): 69-77.

URL:

https://manu60.magtech.com.cn/biotech/10.13523/j.cb.2310055     OR     https://manu60.magtech.com.cn/biotech/Y2023/V43/I12/69

Fig.1 Differences in immune checkpoints between AML and healthy individuals
Fig.2 Differences in immune checkpoint expression between AML patients with different subtypes and healthy individuals
Fig.3 PD-L1 expression and survival analysis
Fig.4 Differential gene volcano map
Fig.5 Pathway enrichment analysis
临床特征 N=24
性别(男,%) 14(58.3)
年龄/岁 63(32~84)
WBC(×109/L) 6(0.49~113.7)
PLT(×109/L) 35.5(3~386)
HGB(×109/L) 65.6(36~108)
LDH 298.28(29~1 909)
β2-MG 1970(8.5~5 917)
脾脏长度/cm 10.8(8.3~22.8)
WT1/% 20(0~78)
骨髓原始细胞(×109/L) 50(12~93)
CD4+PD-1+细胞占淋巴细胞比例/% 8.93(0.42~25.9)
CD8+PD-1+细胞占淋巴细胞比例/% 11.02(0.9~38.14)
骨髓异常细胞PD-L1表达率/% 19.28(0~66.1)
纤维化等级
0~1(n,%) 20(83.3%)
2~3(n,%) 4(16.7%)
异常核型(n,%) 18(75%)
难治复发(n,%) 7(29.1%)
t-AML(n,%) 9(37.5%)
预后
良好(n,%) 2(8.3%)
中等(n,%) 9(37.5%)
差(n,%) 13(54.2%)
Table 1 General characteristics of AML patients
Fig.6 Clinical characteristics affecting PD-L1 expression
Fig.7 Correlation between PD-1 expression and spleen length
Fig.8 Survival differences in groups with different levels of PD-L1 expression
Fig.9 Survival differences in the proportion of CD4+PD-1+cells to lymphocytes with high expression
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