Epigenetic Silencing of CD9 Shapes a New Mechanism to Render Differentiation Block and Immune Evasion in Pediatric Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by clonal expansion of myeloid progenitor cells with impaired terminal differentiation. Despite intensive treatment regimes, the clinical outcomes remain suboptimal. Emerging evidence suggest myeloblasts could evolve multiple machineries to evade immune patrol and hinder immunotherapies. Here, we present a new mechanism involving the tetraspanin protein CD9 in orchestrating differentiation arrest and immune escape in pediatric AML. We first examined CD9 expression and its prognostic impact in patient cohorts of childhood leukemia. The expression of CD9 on blasts of AML patients (12.2%, n=82) was significantly lower than those of ALL patients (90.4%, n=219, P