Histone lysine methylation regulates gene expression and cancer initiation. 
Bioinformatics analysis suggested that DOT1L, a histone H3-lysine79 (H3K79) 
methyltransferase, plays a potentially important role in breast cancer. DOT1L 
inhibition selectively inhibited proliferation, self-renewal, metastatic 
potential of breast cancer cells and induced cell differentiation. In addition, 
inhibitors of S-adenosylhomocysteine hydrolase (SAHH), such as neplanocin and 
3-deazaneplanocin, also inhibited both H3K79 methylation and proliferation of 
breast cancer cells in vitro and in vivo. The activity of SAHH inhibitors was 
previously attributed to inhibition of H3K27 methyltransferase EZH2. However, 
inhibition of EZH2 by a specific inhibitor did not contribute to cell death. 
SAHH inhibitors had only weak activity against H3K27 methylation and their 
activity is therefore mainly due to DOT1L/H3K79 methylation inhibition. Overall, 
we showed that DOT1L is a potential drug target for breast cancer.