Only SF3B1 Mutation involving K700E (And Not Other Codons), Independently Predicts Overall Survival in Myelodysplastic Syndromes [article]

Rashmi Kanagal-Shamanna, Guillermo Montalban-Bravo, Koji Sasaki, Elias Jabbour, Carlos Bueso-Ramos, Yue Wei, Kelly S Chein, Tapan M Kadia, Farhad Ravandi, Gautam M Borthakur, Kelly A Soltysiak, Naval G Daver (+7 others)
2020 bioRxiv   pre-print
SF3B1 mutations (SF3B1mut) in myelodysplastic syndromes (MDS) frequently involve codon K700E and have a favorable prognosis. The prognostic effect of non-K700E SF3B1mut is uncertain. Methods: We analyzed the clinical-pathologic features and outcomes of a single-institutional series of 94 SF3B1mut and 415 SF3B1wt newly diagnosed untreated MDS patients and explored the differences between K700E and non-K700E subgroups. Findings: Ninety-four (19%) patients had SF3B1mut: median age, 74 years.
more » ... five (60%) patients carried K700E. Recurrent non-K700E mutations (39, 40%) included R625, H662 and K666. Compared to SF3B1mut K700E, non-K700E patients had a lower median ANC (1.8 vs. 2.4, p=0.005) and were frequently high R-IPSS (revised International Prognostic Scoring System) [7(19%) vs. 2(4%), p=0.031]. Non-K700E MDS frequently associated with RUNX1 (26% vs. 7%, p=0.012) and exclusively with BCOR, IDH2, and SRSF2 mutations. There was no significant difference in karyotype or SF3B1 variant allele frequency. Most (~80%) were treated with hypomethylating agents. SF3B1mut had superior overall survival (OS) than SF3B1wt in all MDS categories [not-reached vs. 25.2 months, p=0.0003], low-grade MDS, and MDS with ring sideroblasts (MDS-RS). Compared to SF3B1wt, SF3B1mut K700E had superior outcomes in all MDS categories (25 months vs. not-reached, p=0.0001), low-grade MDS, and MDS-RS, but no significant difference was seen with non-K700E. By multivariate analysis, absence of SF3B1mut K700E (not non-K700E) independently associated with prognosis. Interpretation: SF3B1mut MDS show distinct clinical and mutational profiles, with K700E showing a significantly better OS compared to non-K700E mutations and SF3B1wt. Our study highlights the importance of SF3B1 mutation type in MDS risk assessment. Funding: This work was supported by grants from the Ladies Leukemia League, the National Institutes of Health (CA016672) and the MD Anderson MDS/AML Moon Shot.
doi:10.1101/2020.09.04.283598 fatcat:vgrs5tqgrzhetk53lyf4qzalyq