The Leucegene AML surfaceome atlas: immunotherapeutic target identification in AML

We exploited the extensive genomic diversity of the Leucegene cohort of primary human AML specimens to provide an overview of the human AML surfaceome. Due to high cell number requirements, surface proteomics has been underexploited in AML so far, although surface proteome analysis of AML cell lines and small cohorts of primary human AML specimens paved the way for antigen identification23-25. Herein, we compared global and surface proteomic datasets generated from primary human AML specimens and show that surfaceome analysis uniquely identifies a larger subset of cell surface proteins compared to global proteomics. We therefore built a cohort of 100 primary human AML specimens that was subjected to surface proteome analysis and served as a primary dataset for antigen identification. A significant portion of the cohort also underwent single-cell RNA sequencing, which allowed the exploration of antigen expression at the population level and the selection of AML antigens expressed by primitive blasts. These analyses led to the identification of novel AML antigens expressed by the majority of AML specimens of the cohort, of antigens overexpressed by specific AML subgroups, as well as of previously uncovered potential leukemia stem cell (LSC) markers, and represents the first large-scale surface proteomic study in AML.