Epigenetic regulation of abnormal hematopoiesis in MDS
EvansMDS Young Investigator Award
The three-dimensional chromatin structure in MDS patients carry frequent mutations in genes involved in epigenetic modification, especially genes involved in DNA methylation pathways. These mutations impact the DNA methylation landscape in the MDS hematopoietic stem cells (HSC). Additionally, they may also impact the three-dimensional (3D) chromatin structure in MDS by the alterations of DNA methylation. We have found that DNA Methylation Canyons (long genomic regions lacking DNA methylation-DMC for abbreviation) form strong 3D chromatin interactions, specifically in normal HSCs. Because mutations in DNA methylation associated genes could alter the methylation status of DMC, we want to explore how DMC interactions change in the HSC from MDS patients with mutations in DNA methylation associated genes. We would also like to explore how these 3D DMC interaction changes are associated with drug responses in MDS patients. This can provide new insight into how the demethylation agents work in MDS patients – especially for those with mutations in DNA methylation associated genes. Importantly, the dissection of DMC interaction in MDS HSC will provide a new insight into future MDS drug development.