BACKGROUND: Myelodysplastic syndromes (MDS) are a group of blood disorders associated with defective blood cell production and differentiation. In approximately 30 percent of cases, MDS has a chance of progressing into acute myeloid leukemia, which is a type of blood cancer. Important hallmarks of MDS are abnormal DNA promoter methylation and aberrant mRNA alternative splicing. Both activities could lead to the silencing of important tumor suppressor genes which accelerates the disease progression.
OBJECTIVE: The study focused on investigating the possible relationship between DNA methylation level and alternative splicing activity in the hope of targeting the two critical factors of MDS simultaneously. There is currently no cure for MDS, and the result could be useful in developing a novel therapy.
METHODS: The myeloid cell line K562 was either treated with 1)demethylating agent 5’-Azacytidine (AZA) or 2) splicing inhibiting agent Pladienolide B (PB) and their effect on alternative splicing and DNA methylation level were explored respectively. The DNA methylation level and the alternative splicing activity of the drug treated cells were assessed through DNA methylation dot blot assay and the fluorescent microscope images respectively.
RESULTS: The inhibition of DNA methylation could lead to a decrease in splicing activity and the inhibition of splicing might also lead to a decrease in DNA methylation suggesting a positive correlation between the two activities.
CONCLUSIONS: The study was successful in discovering a possible presence of interconnection between the two critical activities related to the pathogenesis of MDS. Further studies are still needed to examine the exact mechanism of how one activity could impact the other. / 2026-02-14T00:00:00Z
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/48120 |
| Date | 15 February 2024 |
| Creators | Cho, Soomin |
| Contributors | Franzblau, Carl, Di Ruscio, Annalisa |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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