Hidden RNA markers could predict blood cancer progression years ahead
Researchers identified a group of overlooked RNA molecules that accumulate abnormally in myelodysplastic neoplasms and signal which patients will progress to leukemia within three years. The discovery could transform how doctors stratify treatment risk and develop new therapies for these difficult-to-treat blood cancers affecting tens of thousands annually.
Originaltitel: Circular <scp>RNA</scp> expression landscapes in myelodysplastic neoplasms: Associations with mutational signatures and disease progression
Myelodysplastic neoplasms (MDS) are heterogeneous malignancies originating in hematopoietic stem cells. In this explorative study, we carried out ultra-deep total RNA sequencing on FACS-sorted CD34+ bone marrow cells from 71 patients and eight healthy age-matched controls. We investigated the expression of circular RNAs (circRNAs), a group of noncoding RNAs produced by back-splicing of nonadjacent splice sites. Key findings were further explored in an independent cohort of 118 patients with MDS and ring sideroblasts. circRNA abundance was higher in the disease groups than in controls, and different spliceosome mutations were associated with distinct circRNA expression patterns. Expression of the proliferation-related gene MKI67 was negatively correlated with circRNA abundance. High circRNA abundance was associated with a significantly increased risk of disease progression at 3 years. The majority of the 38 circRNAs that were significantly upregulated in MDS demonstrated highly correlated expression, and many were associated with risk of leukemic progression. Furthermore, we confirmed the specificity of circZEB1 expression to cases with SF3B1 mutations. We conclude that aberrant circRNA expression is found in MDS and displays associations with disease characteristics and patient outcomes.