LSD1 inhibition induces differentiation of MLL-ENL leukemia cells
YANG Xue-jing1,2, HE Fu-hong1, HUANG Yi-zi3, YAN Jin1, WANG Qian-fei1
1.Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; 2.University of the Chinese Academy of Sciences, Beijing 100049, China; 3. Hunan Agricultural University, Changsha 410128, China
AbstractObjective To investigate the effect of histone demethylase LSD1 inhibition on MLL-ENL leukemia cells. Method An inducible MLL-ENL mouse leukemia cell line Csh3 was used as a model. The cells was first treated with LSD1 inhibitor TCP (Tranylcypromine) . The effect of MLL-ENL cells upon LSD1 inhibition were examined by cell proliferation assay, colony forming cell (CFC) assay and wright-giemsa staining. Furthermore, The global level of histone H3 lysine 4 dimethylation (H3K4me2) and the expression of specific oncogenes and differentiation related genes in MLL-ENL cells were determined using western blotting and RT-PCR respectively. Results LSD1 inhibition significantly reduced cell proliferation and colony growth, and induced cell differentiation in MLL-ENL leukemia cells. Conclusions LSD1 inhibition down-regulated oncogenes expression and up-regulated differentiation related genes to induce MLL-ENL leukemia cells differentiation. LSD1 inhibition may be a promising treatment for MLL-ENL leukemia.