Despite recent advances in immunophenotyping, the prognosis of acute myeloid leukemia (AML) is still mainly estimated using age and genetic markers. As the genetic heterogeneity of AML patients is high, flow cytometry-based classification with appropriate biomarkers can efficiently complement risk stratification and treatment selection. An increased expression of B7-H3 (CD276), an immune checkpoint protein, has been reported and associated with poor prognosis. However, the available data are limited and heterogeneous. Here, we used a novel, proprietary murine anti-B7-H3 8H8 antibody for the flow cytometric analysis of B7-H3 expression in AML blasts from 77 patients. Our antibody reliably detected substantial B7-H3 expression in 62.3% of AML patients. B7-H3 expression was higher in the monocytic French–American–British (FAB) M5 group and in intermediate and poor risk patients according to the European Leukemia Network. Using receiver operating characteristics (ROCs), we identified a specific fluorescence intensity cut-off of 4.45 to discriminate between B7-H3highand B7-H3lowexpression. High B7-H3 expression was associated with shorter overall survival (OS) and progression-free survival (PFS). In conclusion, we have developed a novel B7-H3 antibody that serves as a new tool for the detection of B7-H3 expression in AML and may help to facilitate risk stratification and treatment selection in AML patients.
尽管免疫表型分析技术近期取得进展，急性髓系白血病（AML）的预后评估仍主要依赖年龄和遗传标志物。鉴于AML患者遗传异质性较高，基于流式细胞术的检测结合适当生物标志物可有效补充风险分层与治疗选择。已有研究报道免疫检查点蛋白B7-H3（CD276）表达升高与不良预后相关，但现有数据有限且存在异质性。本研究采用新型专利小鼠抗B7-H3 8H8抗体，对77例AML患者原始细胞的B7-H3表达进行流式细胞术分析。该抗体在62.3%的AML患者中稳定检测到显著的B7-H3表达。根据法美英（FAB）分型，单核细胞型M5组及欧洲白血病网络标准中危/高危患者的B7-H3表达水平更高。通过受试者工作特征曲线分析，我们确定了4.45的特异性荧光强度截断值以区分B7-H3高表达与低表达。高B7-H3表达与较短的总生存期和无进展生存期显著相关。综上，我们开发的新型B7-H3抗体为AML中B7-H3检测提供了新工具，有望促进AML患者的风险分层与治疗选择。
Expression and Prognostic Value of a Novel B7-H3 (CD276) Antibody in Acute Myeloid Leukemia
肿瘤(癌症)患者之家