Abstract
CD81 is a cell surface protein which belongs to the tetraspanin family. While in multiple myeloma its expression on plasma cells is associated with worse prognosis, this has not yet been explored in acute myeloid leukemia (AML). We measured membrane expression of CD81 on AML cells at diagnosis, evaluated its association with AML characteristics and its influence on patient outcome after intensive chemotherapy in a cohort of 134 patients. CD81 was detected in 92/134 (69%) patients. Patients with AML expressing CD81 had elevated leukocyte count (P=0.02) and were more likely classified as intermediate or adverse-risk by cytogenetics (P<0.001). CD81 expression had a negative impact on survival (event-free survival, overall survival and relapse-free survival) in univariate (P<0.001) and in multivariate analyses (P=0.003, 0.002 and <0.001, respectively). CD81 has a negative impact on OS in patients with NPM1 mutation (P=0.01) and in patients ELN-favorable (P=0.002). In conclusion, this cell surface marker may be a new prognostic marker for diagnostic risk classification and a potential therapeutic target for drug development in AML.
Highlights
CD81 antigen belongs to the tetraspanin family (33 members in mammals), which are cell surface transmembrane proteins
Expression of CD81 was found in the majority of acute myeloid leukemia (AML) (92 of 134, 69%), but no CD81 expression was associated with favorable characteristics
AML patients with CD81 positive blast cells were of higher age, had higher white blood cell counts (WBC) at diagnosis (P=0.02) and were more likely to have AML with intermediate or adverse-risk cytogenetics (P
Summary
CD81 antigen belongs to the tetraspanin family (33 members in mammals), which are cell surface transmembrane proteins. This antigen was originally discovered as a target of an antiproliferative antibody and subsequently named TAPA-1 [1]. It associates with other proteins in dynamic membrane entities called tetraspanin-enriched microdomains (TEMs) and partners may vary according to cell type (e.g., CD19 in B cells) [2]. Recent studies showed that tetraspanins are implicated at several stages of carcinogenesis as well as in metastasis and angiogenesis [6]. The prognostic value of CD81 has not been addressed in myeloid malignancies, such as AML
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