肿瘤细胞治疗研究
英文原题：CD84 Expression Across Disease Stages and Leukemic Subpopulations in Acute Myeloid Leukemia.
CD84 Expression Across Disease Stages and Leukemic Subpopulations in Acute Myeloid Leukemia.
结合现有的临床前和临床证据，这些发现支持继续评估靶向CD84的免疫疗法，包括CAR T细胞疗法，在AML中的应用。
背景/目的：近年来，越来越多的证据支持 CD84 作为急性髓系白血病（AML）中有前景的治疗靶点，包括其在 CAR T 细胞治疗中的潜在应用。CD84 在成人和儿童患者的 AML 细胞上均被一致报道为高表达，为开发靶向 CD84 的免疫治疗提供了强有力的生物学依据。方法：我们使用多参数流式细胞术对 61 例成人 AML 患者在诊断时、复发时和难治性疾病时的骨髓和外周血样本中 CD84 的表达进行了表征。结果：我们的结果表明，CD84 在整个疾病过程中均在 AML 细胞上高表达。
BACKGROUND/OBJECTIVES: In recent years, increasing evidence has supported CD84 as a promising therapeutic target in acute myeloid leukemia (AML), including its potential application in CAR T-cell therapy. CD84 is consistently reported to be highly expressed on AML cells in both adult and pediatric patients, providing a strong biological rationale for the development of CD84-directed immunotherapies. METHODS: We characterized CD84 expression in bone marrow and peripheral blood samples from 61 adult patients with AML at diagnosis, relapse, and refractory disease using multiparametric flow cytometry. RESULTS: Our results demonstrate that CD84 is highly expressed on AML cells throughout the course of the disease. More than 80% of leukemic populations showed CD84 expression above 80%, with median expression levels remaining consistently high at diagnosis (98%), relapse (96.5%), and refractory disease (96%). A novel aspect of our study is the evaluation of CD84 expression across distinct leukemic subpopulations within individual samples; only three of the 94 leukemic populations analyzed showed CD84 expression below 20%. Similarly, CD84 expression remained consistently high across the major AML subtypes analyzed, including AML with NPM1 mutation, AML with myelodysplasia-related gene mutations, and TP53-mutated AML. Comparable median CD84 expression was observed in bone marrow and peripheral blood; however, paired analysis identified significant differences between both compartments. CD84 expression assessed with antibody clone 153-4D9 was significantly lower than that detected with clone CD84.1.21 across AML leukemic populations (median, 75% vs. 98%; p < 0.0001). When compared with CD33 and CD123, CD84 showed a similarly broad prevalence of expression across AML leukemic populations. Healthy bone marrow samples were additionally evaluated to characterize the physiological distribution of CD84 expression across normal hematopoietic populations and provide a framework for the assessment of CD84-targeted therapeutic strategies. CONCLUSIONS: Together with the available preclinical and clinical evidence, these findings support the continued evaluation of CD84-directed immunotherapies, including CAR T-cell therapy, in AML.
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