| Summary: | It has been reported that gene mutations in <i>SF3B1</i> and <i>PHF6</i> 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 <i>SF3B1</i> and <i>PHF6</i>, 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. <i>SF3B1</i> mutations were detected in the first analysis of all the patients. <i>PHF6</i> mutations occurred either concurrently with <i>SF3B1</i> 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 <i>ASXL1</i>, <i>RUNX1</i>, <i>TET2</i>, and <i>NRAS</i>. 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 <i>SF3B1</i> and <i>PHF6</i> are rare, but they do exist in a variety of myeloid neoplasms, with roles as early initiating events and in disease progression, respectively.
|
|---|