Abstract:
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-H3high and B7-H3low expression. 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.
摘要:
尽管最近在免疫分型方面取得了进展,急性髓系白血病(AML)的预后仍主要通过年龄和遗传标记进行评估.由于AML患者的遗传异质性高,基于流式细胞术的分类和适当的生物标志物可以有效补充风险分层和治疗选择。B7-H3(CD276)的表达增加,一种免疫检查点蛋白,已被报道并与不良预后相关。然而,可用数据有限且异构。这里,我们用了一本小说,专有鼠抗B7-H38H8抗体,用于流式细胞术分析77例患者AML母细胞中B7-H3表达。我们的抗体在62.3%的AML患者中可靠地检测到大量B7-H3表达。根据欧洲白血病网络,单核细胞法国-美国-英国(FAB)M5组和中等和低风险患者中B7-H3表达更高。使用接收器工作特性(ROC),我们确定了一个特定的荧光强度截止值4.45,以区分B7-H3high和B7-H3low表达。高B7-H3表达与较短的总生存期(OS)和无进展生存期(PFS)相关。总之,我们开发了一种新型B7-H3抗体,该抗体可作为检测AML中B7-H3表达的新工具,可能有助于促进AML患者的风险分层和治疗选择.