Among some patients with myelodysplastic syndrome (MDS), gene expression signatures appear to be predictive of response and primary resistance to azacitidine, according to research published in Scientific Reports.

MDS, is currently only curable with allogeneic stem cell transplantation. Hypomethylating agents, including azacitidine, are sometimes used as a bridging treatment, prior to transplantation to diminish marrow blasts, though historically, it has been difficult to predict which patients will respond to these agents.

For this study, researchers conducted RNA sequencing using bone marrow samples from patients with advanced MDS and excess blasts prior to azacitidine treatment to determine any factors that might predict a response or treatment resistance. Overall, 23 patients were included, 14 of whom (61%) showed complete remission in marrow tissue and 9 whom (39%) showed primary resistance to azacitidine.

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In patients responding to the bridging treatment, molecular functions representing both mitochondria and apoptosis appeared to be upregulated. Among patients who did not respond to azacitidine, several genes in the Wnt pathway were upregulated. In independent validation cohorts these distinguishing features between responders and nonresponders accurately predicted both azacitidine response and favorable prognosis.

UBC and PFDN2, which are involved in ubiquitination,also appeared to predict a treatment response.

“Comparison of gene expression profiles between 14 responders and 9 [nonresponders] revealed a number of molecular functions (e.g., apoptosis and cellular respiration) were relatively activated in responders,” the authors wrote. “Functional scores of these molecular pathways were also correlated with patient survival in an independent MDS cohort, and the results suggested their potential prognostic value,” concluded the investigators.


Kim K, Park S, Choi H, et al. Gene expression signatures associated with sensitivity to azacitidine in myelodysplastic syndromes. Sci Rep. 2020;10(1):19555. doi:10.1038/s41598-020-76510-7