JAK2, CALR, and MPL are myeloproliferative neoplasm (MPN)-driver mutations, 
whereas SF3B1 is strongly associated with ring sideroblasts (RS) in 
myelodysplastic syndrome (MDS). Concomitant mutations of SF3B1 and MPN-driver 
mutations out of the context of MDS/MPN with RS and thrombocytosis 
(MDS/MPN-RS-T) are not well-studied. From the cases (<5% blasts) tested by NGS 
panels interrogating at least 42 myeloid neoplasm-related genes, we identified 
18 MDS/MPN-RS-T, 42 MPN, 10 MDS, and 6 MDS/MPN-U cases with an SF3B1 and an 
MPN-driver mutation. Using a 10% VAF difference to define "SF3B1-dominant," 
"MPN-mutation dominant," and "no dominance," the majority of MDS/MPN-RS-T 
clustered in "SF3B1-dominant" and "no dominance" regions. Aside from parameters 
as thrombocytosis and ≥15% RS required for RS-T, MDS also differed in frequent 
neutropenia, multilineage dysplasia, and notably more cases with <10% VAF of 
MPN-driver mutations (60%, p = 0.0346); MPN differed in more frequent 
splenomegaly, myelofibrosis, and higher VAF of "MPN-driver mutations." "Gray 
zone" cases with features overlapping MDS/MPN-RS-T were observed in over 
one-thirds of non-RS-T cases. This study shows that concomitant SF3B1 and 
MPN-driver mutations can be observed in MDS, MPN, and MDS/MPN-U, each showing 
overlapping but also distinctively different clinicopathological features. 
Clonal hierarchy, cytogenetic abnormalities, and additional somatic mutations 
may in part contribute to different disease phenotypes, which may help in the 
classification of "gray zone" cases.