Abstract
Dexamethasone (Dex), a synthetic glucocorticoid that acts by binding to
the glucocorticoid receptor (GR),
has been widely applied to treat leukemia and lymphoma, however the
precise mechanism underlying Dex action is still not well elucidated.
DOT1L, a histone H3-lysine79 (H3K79) methyltransferase, has been linked
to multiple cancer types, particularly mixed lineage leukemia (MLL) gene
rearranged leukemia, but its contribution to lymphoma is yet to be
delineated. Analysis from TCGA database displayed that DOT1L was highly
expressed in lymphoma and leukemia. In the present study, we initially
demonstrated that DOT1L served as a newly target gene controlled
by GR, and downregulation of DOT1L was critical for the killing
of B lymphoma cells by Dex. Further study revealed that Dex had no
impact on the transcriptional activity of DOT1L promoter, rather
it reduced the mRNA level of DOT1L through decreasing mRNA
stability. In addition, knockdown ofDOT1L remarkably inhibited the B lymphoma cells growth. Overall,
our findings indicated that DOT1L may serve as a potential drug target
and a promising biomarker of Dex sensitivity when it comes to treating B
lymphoma.