Circular RNA Expression Linked to Disease Progression in MDS

High circular RNA (circRNA) abundance is correlated with disease progression in patients with myelodysplastic syndromes (MDS), according to a study presented at the European Hematology Association 2024 Hybrid Congress in Madrid, Spain.

The study, led by Eileen Wedge, MD, of the University of Copenhagen in Denmark, explored the relationship between circRNA abundance and cellular dynamics in MDS hematopoietic stem and progenitor cells (HSPCs).

The researchers performed total RNA sequencing on HSPCs from two cohorts:

• The mixed MDS cohort, which included 45 patients with a mix of MDS subtypes plus eight healthy controls
• The ring sideroblast cohort, which included 118 patients with MDS with ring sideroblasts plus 10 healthy controls

In the mixed MDS cohort, high circRNA expression was associated with a “significantly increased risk” of disease progression (P=.021). Most upregulated circRNAs had a “highly correlated expression,” with a tendency for samples to cluster by spliceosome mutation, particularly SF3B1. CircZEB1 was specifically expressed in patients harboring SF3B1 mutations.

In the ring sideroblast cohort, high circZEB1 expression was correlated with worse overall survival in patients with SF3B1 mutations.

CircRNA abundance was significantly correlated with MKI67 expression in both the mixed MDS cohort (r=0.471; P=.001) and the ring sideroblast cohort (r=0.432; P<.0001). BCL2 expression was associated with circRNA abundance in the mixed MDS cohort, but not in the ring sideroblast cohort. In both cohorts, Molecular International Prognostic Scoring System score was positively correlated with circRNA abundance and negatively correlated with MKI67 expression.

“These findings can help generate hypotheses for further research on the biology of MDS and the significance of circRNAs in this disease,” concluded Dr. Wedge and colleagues.

Reference

Wedge E, Tulstrup M, Todisco G, et al. Circular RNA expression in myelodysplastic syndrome HSCPs is associated with the expression of proliferation markers and risk of disease progression. Abstract #P1882. Presented at the European Hematology Association 2024 Hybrid Congress; June 13-16, 2024; Madrid, Spain.