KEY TAKEAWAYS
- The study aimed to investigate the role of DOT1L in mediating the effects of Dex on B-lymphoma cell growth and its potential as a therapeutic target.
- The study concluded that DOT1L is a potential drug target and biomarker for Dex sensitivity in B lymphoma treatment.
Pexamethasone (Dex), a synthetic glucocorticoid that binds to the glucocorticoid receptor (GR), is commonly used to treat leukemia and lymphoma. However, the exact mechanisms by which Dex exerts its effects remain poorly understood. DOT1L, a histone H3-lysine79 (H3K79) methyltransferase, has been associated with various cancer types, particularly mixed lineage leukemia (MLL) gene-rearranged leukemia; however, its role in lymphoma has yet to be clearly defined. Analysis from the TCGA database revealed that DOT1L is highly expressed in both lymphoma and leukemia.
Yuting Wang and the team aimed to assess the impact of DOT1L on the growth of B-lymphoma cells and its potential as a therapeutic target for enhancing Dex sensitivity.
It was initially demonstrated that DOT1L acts as a novel target gene regulated by GR, with the downregulation of DOT1L being crucial for the elimination of B-lymphoma cells by Dex. Further investigation revealed that Dex did not affect the transcriptional activity of the DOT1L promoter; instead, it decreased the mRNA level of DOT1L at the posttranscriptional level. Additionally, the knockdown of DOT1L significantly inhibited the growth of B-lymphoma cells.
The study concluded that DOT1L may serve as a potential drug target and a promising biomarker for Dex sensitivity in the treatment of B lymphoma.
This study was funded by the National Natural Science Foundation of China (No. 81470325).
Source: https://pubmed.ncbi.nlm.nih.gov/39307938/
Wang Y, Zhang N, Shang W, et al. (2024). “Dexamethasone Inhibits the Growth of B-Lymphoma Cells by Downregulating DOT1L.” Cancer Rep (Hoboken). 2024;7(9):e2150. doi:10.1002/cnr2.2150
