What Is the Role of Splicing Mutations in Patients with Myelofibrosis?

Among high-risk splicing mutations (SPM), SRSF2 has the worst prognostic role in patients with myelofibrosis, secondary to polycythemia vera and essential thrombocytopenia (PPV-MF, PET-MF), according to a recent study.

Led by Julie Braish, MBBS, of the University of Texas MD Anderson Cancer Center, the study assessed the role of SPM on the survival outcome of patients with PPV/PET-MF, as well as how SPM interact with other high-risk molecular mutations (HMR).

The researchers retrospectively reviewed the medical charts of 114 patients with MF who had SPM. SRSF2 and SF3B1 were the most common SPM (41.0% each), followed by U2AF1 (17.5%) and ZRSR2 (11.0%). Six patients had more than one SPM.

SRSF2 mutations were more present in patients with primary myelofibrosis (PMF), while SF3B1 mutations were more present in patients with PET/PPV-MF. However, the distribution of SPM types did not statistically differ.

The researchers detected HMR in 77 (68%) patients; ASXL1 was the most common (65%), followed by EZH2 (19%) and IDH1/2 (16%). ASXL1 co-occurred more frequently with SF3B1 in PET/PPV-MF patients (75% vs 25%, respectively) and more frequently with SRSF2 (62% vs 38%) and U2AF1 (89% vs 11%) in PMF patients.

The median overall survival (OS) for SRSF2 and SF3B1 was 46 months and 130 months, respectively, while the median OS for U2AF1 and ZRSR2 was not reached. The median OS for high-risk SPM with and without HMR and low-risk SPM with and without HMR was 46 and 51 months versus 109 and 130 months, respectively.

The researchers determined that various SPM have similar effects on the survival of PET/PPV-MF and PMF patients, and that the co-occurrence of HMR does not appear to impact survival outcome.

“Further validation of our data, including association with received therapy, is ongoing,” wrote Dr. Braish and colleagues.

Reference

Braish J, Bose P, Pemmaraju N, et al. Deeper insight into splicing mutations in myelofibrosis. Abstract #4580. Presented at the 65th ASH Annual Meeting & Exposition; December 9-12, 2023; San Diego, California.