IMAGE: 5-AZA-sensitive and 5-AZA-resistant leukemia cells have distinctly different chromatin structures. view more
Credit: Jason Cheng
Drug resistance is a major obstacle to effective treatment for patients with cancer and leukemia. Epigenetic modifying drugs have been proven effective for some patients with hematologic malignancies, such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Unfortunately, most patients treated with epigenetic modifying drugs develop resistance, resulting in therapeutic failure and eventually, patient death. The mechanisms underlying the selectivity and resistance of epigenetic modifying drugs remain largely elusive.
A research team based at the University of Chicago has begun to unravel the role of RNA epigenetics and chromatin structure in regulation of 5-azacytidine (5-AZA), a well-known DNA hypomethylating agent in MDS and AML. The finding may lead to novel strategies, as well as guidance from clinical biomarkers that could help predict and reduce the risk of drug resistance, a major obstacle in leukemia treatment.
“This is the first study to demonstrate that RNA cytosine methylation and methyltransferases mediate cell lineage-associated drug-responsive chromatin structures in MDS and AML,” said the study’s lead author, Jason Cheng, MD, PhD, assistant professor of pathology at the University of Chicago.
“This is a new area,” he
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