Journal
ANALYTICAL BIOCHEMISTRY
Volume 442, Issue 1, Pages 104-106Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ab.2013.07.032
Keywords
LSD1; CD86; Acute myeloid leukemia; Inhibitors; Assay; Biomarker
Funding
- Cancer Research UK [C5759/A12328, C5759/A11411]
- Leukemia and Lymphoma Research Clinical Training Fellowship
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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 24 h 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. (C) 2013 Elsevier Inc. All rights reserved.
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