DNA Methylation May Help Predict Treatment Response in Myelodysplastic Syndromes
Posted on 10 Nov 2026
Myelodysplastic syndromes (MDS) are disorders in which the bone marrow does not produce healthy blood cells normally. Treatment selection can be challenging because clinicians cannot reliably predict which patients will respond to therapy. DNA methyltransferase inhibitors such as azacitidine are used to treat MDS, but dependable biomarkers of treatment response have been lacking. New findings now suggest that DNA methylation patterns present at diagnosis may help predict response to azacitidine.
Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, participated in a multicenter study evaluating DNA methylation as a predictive marker in myelodysplastic syndromes (MDS). The research focused on DNA methylation patterns present at diagnosis and their relationship to response to azacitidine, a commonly used therapy for MDS. The findings were published in the Journal of Clinical Investigation.
DNA methylation involves chemical marks on DNA that help regulate whether genes are turned on or off without changing the underlying DNA sequence. Because altered DNA methylation is a hallmark of MDS, the researchers examined these patterns alongside DNA mutations, gene activity, and clinical information. Using the combined data, they developed computational models designed to predict response to azacitidine.
The researchers analyzed DNA mutations, DNA methylation, and gene activity in 98 patients with MDS. Patients were grouped according to their DNA methylation patterns, and the predictive models were then tested in an independent patient cohort. The analysis identified seven groups with distinct biological characteristics.
DNA methylation proved more informative than gene activity alone for predicting treatment response. Some of the strongest predictive signals were found in regulatory regions outside the parts of the genome that researchers have traditionally emphasized. In one group, identified as Cluster VI and characterized by relatively few DNA mutations, 71% of patients responded to azacitidine.
The study suggests that biological features present at diagnosis may help identify patients most likely to benefit from azacitidine therapy. However, further research is needed before DNA methylation patterns can be used to guide routine clinical care. The findings also indicate that incorporating epigenetic information may provide a broader understanding of treatment response in MDS.
“These findings suggest that the epigenetic features of the disease could provide information we have not been able to capture with conventional approaches,” said Maria “Ken” Figueroa, M.D., Sylvester researcher, associate director of translational research and the study’s co-lead.
“Our goal is to turn a better understanding of MDS into better guidance for patients, so they can face treatment with greater confidence in the path ahead,” said Mikkael Sekeres, M.D., M.S., chief and professor of hematology at Sylvester and co-lead of the study.
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