Splicing Factor 3B Subunit 1 Mutations in Myelofibrosis

In a presentation at the 2022 American Society of Clinical Oncology Annual Meeting, Prithviraj Bose and colleagues reported that mutations in splicing factor 3B subunit 1 (SF3B1) are an uncommon occurrence in patients with myelofibrosis and do not appear to substantially affect outcomes and disease phenotype.

This finding is distinct from the effects of SF3B1 mutations in other myelodysplastic syndromes and myeloproliferative neoplasms, where they indicate a “unique phenotype” with a favorable prognosis, according to Dr. Bose.

The study retrospectively analyzed 381 patients with World Health Organization (WHO)-defined myelofibrosis who visited the authors’ center from January 2017 to July 2021. Patients with either SF3B1-mutated or SF3B1-wild type myelofibrosis were compared on the following variables: disease phenotype, myeloproliferative neoplasms driver and co-occurring mutations, cytogenetics, dynamic International Prognostic Scoring System (IPSS) score, transfusion requirements, treatment characteristics, and survival outcomes.

Of the 381 patients, 29 (8%) were SF3B1-mutated, with K666N being the most common mutation (52%). Overall frequencies of JAK2, CALR, MPL mutations, and triple negative myelofibrosis were similar between the SF3B1-mutated and non-mutated groups. Notably, more SF3B1-mutated patients were PRBC transfusion-dependent at presentation that non-mutated patients.

Ultimately, the authors concluded that SF3B1 mutations are rare in patients with myelofibrosis and, except for PRBC transfusion dependence, most measures between mutated and non-mutated groups were relatively similar.