CD86 expression as a surrogate cellular biomarker for pharmacologic inhibition of the histone demethylase LSD1.

Abstract

There is a lack of rapid cell-based assays that read out enzymatic inhibition of the histone demethylase LSD1. Through transcriptome analysis of human acute myeloid leukemia THP1 cells treated with a tranylcypromine-derivative inhibitor of LSD1 active in the low nanomolar range, we identified the cell surface marker CD86 as a sensitive surrogate biomarker of LSD1 inhibition. Within 24 hours of enzyme inhibition there was substantial and dose-dependent up regulation of CD86 expression, as detected by quantitative PCR, flow cytometry and ELISA. Thus, use of CD86 expression may facilitate screening of compounds with putative LSD1 inhibitory activities in cellular assays.