Concurrent Mutations in and in Myeloid Neoplasms.

It has been reported that gene mutations in and are mutually exclusive. However, this observation has never been rigorously assessed. We report the clinicopathologic and molecular genetic features of 21 cases of myeloid neoplasms with double mutations in and , including 9 (43%) with myelodysplastic syndrome, 5 (24%) with acute myeloid leukemia, 4 (19%) with myeloproliferative neoplasms, and 3 (14%) with myelodysplastic/myeloproliferative neoplasms. Multilineage dysplasia with ring sideroblasts, increased blasts, and myelofibrosis are common morphologic findings. All cases but one had diploid or non-complex karyotypes. mutations were detected in the first analysis of all the patients. mutations occurred either concurrently with mutations or in subsequent follow-up samples and are associated with disease progression and impending death in most cases. Most cases had co-mutations, the most common being , , , and . With a median follow-up of 39 months (range, 3-155), 17 (81%) patients died, 3 were in complete remission, and 1 had persistent myelodysplastic syndrome. The median overall survival was 51 months. In summary, concurrent mutations in and are rare, but they do exist in a variety of myeloid neoplasms, with roles as early initiating events and in disease progression, respectively.