Abstract
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.