Analysis of myeloid neoplasms with isolated trisomy 19 reveals a novel MDS subgroup characterized by the presence of ring sideroblasts, fibrosis and SRSF2 and/or ASXL1 mutations.

We collected 97 cases of myeloid neoplasia with the rare cytogenetic event of isolated trisomy 19 (+19), with the aim to characterize this group clinically and pathologically. 51 patients with myelodysplastic syndrome (MDS +19) and 11 patients with myelodysplastic/myeloproliferative neoplasms (MDS/MPN +19) presented with +19 at disease onset and were further analyzed. Patients with insufficient data were excluded. We collected additional clinical and laboratory data and performed mutation analysis on available bone marrow biopsies. The 62 patients of both disease groups turned out to be remarkably homogeneous in terms of male sex (85%), the presence of anemia with increased numbers of ring sideroblasts (RS, 80%), the absence of an SF3B1 mutation (95%), and the overall rather consistent presence of SRSF2 (61%) or ASXL1 (39%) mutations. MDS +19 patients with available follow-up (1 month to 7.5 years) presented or progressed with significant fibrosis (45%), leuko- or monocytosis (13%) or acute leukemia (28%). Compared to a control cohort of 23 patients with MDS and an SRSF2 mutation, but without isolated +19 (MDS-SRSF2), the 16 MDS +19 patients with SRSF2 mutation and the 12 MDS +19 patients with an ASXL1 mutation showed a striking difference in the presence of ≥ 15% RS (73% and 67% versus 17% in MDS-SRSF2) and the occurrence of fibrosis (44% and 57% versus 4% in MDS-SRSF2). Although all individual features observed in the MDS +19 and MDS/MPN +19 cohorts are seen in MDS and MDS/MPN in general, their combination is rather unique and provides clues regarding disease evolution in this rare, cytogenetically defined group of myeloid neoplasia.