Predicting Azacitidine Response in Myelodysplastic Syndromes
DNA methylation patterns present at the time of diagnosis can help predict how patients with myelodysplastic syndromes will respond to azacitidine, according to a multicenter study published in the Journal of Clinical Investigation.
Choosing a treatment for myelodysplastic syndromes, or MDS, involves a stubborn clinical challenge. Doctors cannot reliably predict which patients will respond to therapy.
Researchers at Sylvester Comprehensive Cancer Center investigated whether DNA methylation patterns at diagnosis help predict the response to azacitidine. The study was published in the Journal of Clinical Investigation, with doi: 10.1172/JCI208317.
Researchers Identify Seven Biological Clusters in MDS Patients
The research team analyzed DNA mutations, DNA methylation, and gene activity in 98 patients diagnosed with MDS. Investigators grouped the patients based on distinct biological features.
The analysis identified seven distinct groups. One specific subset, referred to as Cluster VI, was characterized by having relatively few DNA mutations. In that particular group, 71% of patients responded to azacitidine treatment.
DNA methylation proved more useful than gene activity alone for predicting treatment response. Some of the strongest predictive signals originated from regulatory regions beyond the parts of DNA researchers traditionally focus on.
The research team integrated DNA methylation data with gene expression, mutations, and clinical information to develop their predictive model. The team then tested these models in an independent patient group to ensure robustness.
Unlocking Epigenetic Features Before Therapy Begins
“Our goal is to get closer to answering one of the most important questions for a patient at diagnosis. Which treatment is most likely to work for them?” Maria “Ken” Figueroa stated. Dr. Figueroa is a Sylvester researcher and co-lead of the study.
“These findings suggest that the epigenetic features of the disease could provide information we have not been able to capture with conventional approaches,” Dr. Figueroa added.
“One of the Holy Grails of treating cancer is to determine whether or not a therapy will work before we even get started,” Mikkael Sekeres said. Dr. Sekeres is chief and professor of hematology at Sylvester and co-lead of the study.
“While further research will be needed before these findings can guide routine care, this is a step in the right direction,” Dr. Sekeres stated. He also noted that the finding offers a step toward more informed treatment decisions.
Further research is required before these findings can guide routine clinical care. The study suggests that biological features present at diagnosis could help identify patients most likely to benefit from therapy.
The study builds on Sylvester’s strength in cancer epigenetics, the study of changes in gene regulation that can influence cancer biology.
