Comparison of the clinicopathological features in myeloproliferative or myelodysplastic neoplasms with SF3B1 / JAK2 , SF3B1 / CALR , or SF3B1 / MPL co-mutations

Mutations in JAK2, CALR, and MPL account for over 90% of Philadelphia-negative (Ph-) myeloproliferative neoplasm (MPN), while SF3B1 mutations are diagnostic for myelodysplasia in myelodysplastic syndrome (MDS) or myelodysplastic/myeloproliferative neoplasm (MDS/MPN). Concurrent mutations of SF3B1 with JAK2, CALR, or MPL in myeloid neoplasms have not been extensively studied. We identified a total of 136 cases with SF3B1/JAK2 (SJ), SF3B1/CALR (SC), and SF3B1/MPL (SM) co-mutations and demonstrated that SJ, SC, and SM co-mutations are prevalent across various myeloid neoplasms, with the highest frequency observed in MPN and MDS/MPN, and with SJ representing the most common co-mutation. MDS/MPN with SF3B1 mutation and thrombocytosis shows the strongest overall association with SJ, SC, and SM co-mutations. Primary myelofibrosis shows the strongest association with the three co-mutations within MPN. JAK2 VAF levels differ significantly among MPN, MDS/MPN, and MDS. MDS cases with these co-mutations had significantly poorer overall survival compared to MPN and MDS/MPN cases.