title: CD86 expression as a surrogate cellular biomarker for pharmacological inhibition of the histone demethylase lysine-specific demethylase 1.
abstract: There is a lack of rapid cell-based assays that read out enzymatic inhibition of the histone demethylase LSD1 (lysine-specific demethylase 1). 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 24h of enzyme inhibition, there was substantial and dose-dependent up-regulation of CD86 expression, as detected by quantitative polymerase chain reaction, flow cytometry, and enzyme-linked immunosorbent assay. Thus, the use of CD86 expression may facilitate screening of compounds with putative LSD1 inhibitory activities in cellular assays.
authors.affiliation: Cancer Research UK Leukaemia Biology Laboratory, Paterson Institute for Cancer Research, University of Manchester, Manchester M20 4BX, UK.
authors.forename: James T
authors.initials: JT
authors.lastname: Lynch
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Cockerill
authors.forename: James R
authors.initials: JR
authors.lastname: Hitchin
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Wiseman
authors.forename: Tim C P
authors.initials: TC
authors.lastname: Somervaille
mesh_terms: D051940:B7-2 Antigen / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D056466:Histone Demethylases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013329:Structure-Activity Relationship; D014191:Tranylcypromine / Q000737:chemistry / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D051940:B7-2 Antigen; D015415:Biomarkers; C497964:CD86 protein, human; D004791:Enzyme Inhibitors; D014191:Tranylcypromine; D056466:Histone Demethylases; C495195:KDM1A protein, human
keywords: Acute myeloid leukemia; Assay; Biomarker; CD86; Inhibitors; LSD1