CD84 Expression Across Disease Stages and Leukemic Subpopulations in Acute Myeloid Leukemia.
In samples from 61 adults with AML, multiparametric flow cytometry showed generally high CD84 expression across disease stages, leukemic subpopulations, and major molecular subtypes, while measured expression differed substantially between antibody clones.
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In samples from 61 adults with AML, multiparametric flow cytometry showed generally high CD84 expression across disease stages, leukemic subpopulations, and major molecular subtypes, while measured expression differed substantially between antibody clones.
Research significance
The reported persistence and breadth of CD84 expression support target availability in adult AML; it is reasonable but still inferential to hypothesize that CD84-directed therapies, including CAR T cells, could cover heterogeneous or relapsed AML populations, because this study provides no therapeutic efficacy, safety, or pediatric validation.
Source 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.