The myelodysplastic syndromes (MDS) are common myeloid malignancies characterized by ineffective hematopoiesis and blood cytopenias, with patients showing increasing bone marrow blasts with disease progression [1]. Mutations in genes involved in pre-mRNA splicing (SF3B1, SRSF2, U2AF1, and ZRSR2) are the most common mutations found in MDS, occurring in over 50% of all cases [2–4]. There is evidence that some spliceosome components play a role in the maintenance of genomic stability [5]. Splicing is a transcription coupled process; splicing factor mutations affect transcription and may lead to the accumulation of R-loops (RNA-DNA hybrids with a displaced single stranded DNA)[6]. Mutations in the splicing factors SRSF2 and U2AF1 have been recently shown to increase R-loop formation in leukemia cell lines, resulting in increased DNA damage, replication stress, and activation of the ATR-Chk1 pathway [7, 8]. SF3B1 is the most frequently mutated