Among patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML), plasma citrate levels and CD34-positive cells–transcriptional signatures linked with cycling status may predict whether a patient responds to azacitidine, according to research published in Cancers (Basel).
Patients with high-risk MDS, AML, or AML with myelodysplasia-related changes are frequently treated with hypomethylating agents (HMA), including azacitidine and decitabine. While these treatments have improved outcomes, only approximately 50% of patients respond to HMA therapy, and overall patient prognoses remain poor.
It has, therefore, become increasingly important to attempt to identify which patients are the most and least likely to respond to HMA therapy. Analyses of epigenetic mutations have shown promise in predicting response, though previous study results are not completely accepted. For the present study, researchers attempted to confirm the findings of previous epigenetic analyses, and to determine other factors likely to predict response, or non-response, to HMA treatment.
Specimens from 25 patients with MDS or AML with myelodysplasia-related changes were included in this study; 11 peripheral blood plasma samples were also analyzed. All patients received azacitidine; 10 responded, 6 had stable disease, and 9 had progressive disease. CD34-positive cells from 8 control individuals were analyzed for comparison.
Analysis showed that, compared with controls and responders, the transcriptional landscapes of CD34-positive hematopoietic stem/progenitor cells in patients with progressive disease showed decreased signatures of active cell cycling, as well as DNA damage.
IDH2 was, furthermore among the downregulated genes noted in patients with progressive disease, contrasting further with responders. CD34-positive cell cycle quiescence signatures were also noted in non-responders.
Overall, the findings confirmed previous epigenetic analyses of the transcriptional landscapes in CD34-positive hematopoietic stem/progenitor cells between responders/controls and those with progressive disease.
Koralkova P, Belickova M, Kundrat D, et al. Low plasma citrate levels and specific transcriptional signatures associated with quiescence of CD34+ progenitors predict azacitidine therapy failure in MDS/AML patients. Cancers (Basel). 2021;13(9):2161. doi:10.3390/cancers13092161