1. Introduction
Glucocorticoid is widely used due to its effective anti-inflammatory and immunosuppressing effect [1] . Dexamethasone (Dex), a classical glucocorticoid, is recognized as one of the standard therapeutics in hematological malignancies including leukemia and lymphoma, and the clinical effect is much better than other Glucocorticoids [2-4]. Dex exerts its anti-tumor effects primarily by binding to and subsequently activating glucocorticoid receptor (GR) [5, 6]. After translocating into the nuclear region, activated GR commonly regulates the expression of its target genes via binding to the glucocorticoid response element (GRE) [7, 8]. Although the function of GR has been studied for decades, its precise antitumor mechanism has not been clearly clarified yet.
DOT1L (disruptor of telomere silencing 1 like) is the sole methytransferase which carries out the methylation of histone H3 at lysine 79 [9]. Previous research have reported that DOT1L is linked to multiple biological processes, such as telomere silencing, gene expression regulation, cell aging, and DNA damage response [10-12]. Recently, it has been proved that DOT1L has a crucial role in the initiation and progression of various tumour types, such as lung cancer, breast cancer, ovarian cancer, renal clear cell carcinoma, and neuroblastoma [13-16]. Notably, DOT1L is strongly correlated with MLL-rearranged leukemia [17]. DOT1L leads to aberrant H3K79 methylation that contributes to the overexpression of MLL target oncogenes such asMEIS1 and HOXA9 . Therefore, DOT1L is considered as a newly therapeutic target against MLL-rearranged leukemia and the corresponding inhibitors are investigating in clinical trials [18-20]. However, it remains elusive whether DOT1L is linked to B cell lymphoma and whether DOT1L can be regulated by Dex.
Our work shows that DOT1L plays an oncogenic role in B lymphoma cells and Dex downregulates DOT1L via GR activation. Besides, Dex decreases DOT1L expression in Dex-sensitive B lymphoma cells and MLL-rearranged leukemia cells, but not in Dex-insensitive acute monocytic leukemia cells, suggesting that DOT1L may be a underlying novel indicator of Dex sensitivity against hematological malignancies.