Comparison of therapy-related myelodysplastic syndrome with ring sideroblasts and de novo myelodysplastic syndrome with ring sideroblasts

摘要

Presence of RS is closely associated with SF3B1 mutation in de novo MDS. RS is also present in a subset of therapy-related MDS (t-MDS), but data is not available in t-MDS with RS (t-MDS-RS). Using NGS gene panel, we assessed t-MDS-RS (n = 38) and compared the result with d-MDS-RS (n = 174). Commonly mutated genes were TP53 (56.5%), TET2 (39.1%), SF3B1 (35.7%), ASXL1 (30.4%), DNMT3A (17.4%), RUNX1 (17.4%) and SRSF2 (14.3%). Compared with d-MDS-RS, TP53 mutation was more common but SF3B1 mutation was less common in t-MDS-RS (p < 0.05). In t-MDS-RS, Mutations in 4 genes (SF3B1, U2AF1, SRSF2 and ZRSR2) involving the RNA splicing were found in about 50% of patients compared to (similar to)90% in d-MDS-RS. Overall survival was by far worse in t-MDS-RS compared to d-MDS-RS (median overall survival: 10.9 months and 111.9 months in t-MDS-RS and d-MDS-RS, respectively, p < 0.05). Progression to acute myeloid leukemia was more common in t-MDS-RS (18.4% vs. 7.4% in t-MDS-RS and d-MDS-RS, respectively, p < 0.05). Unlike de novo MDS, t-MDS-RS did not have different outcome compared to t-MDS without RS (median OS: 10.9 months vs. 14.3 months, respectively, p = 0.2341). Our data demonstrate that presence of RS is not associated with superior outcome in t-MDS. Mutation profiles suggest RS in t-MDS might be a secondary event in at least 50% of the cases or not related to mutations in RNA splicing machinery unlike d-MDS where mutations in RNA splicing machinery occur early and as associated with ineffective erythropoiesis.