[Clinical characteristics and prognosis of myelodysplastic neoplasms with GATA2 mutations]

Objective: To investigate the clinical characteristics and prognosis of myelodysplastic neoplasms (MDS) patients with GATA2 mutations. Methods: This was a retrospective cohort study. Clinical data of 1 365 MDS patients who were diagnosed at the Institute of Hematology and Blood Diseases Hospital from September 2016 to August 2024 were collected. Retrospective analysis was conducted to evaluate the clinical features, laboratory characteristics, and overall survival (OS) of MDS patients with GATA2 mutations. Results: ① Among the 1 365 MDS patients, 69 (5.1%) carried pathogenic/likely pathogenic GATA2 mutations, including 14 (1.0%) with germline/likely germline mutations and 47 (3.4%) with somatic mutations. Null variants predominated in the germline/likely germline group [50.0% (7/14) ], whereas missense mutations were common in the somatic group [76.8% (43/56) ]. ② The median age at diagnosis was significantly younger in the germline/likely germline group than in the somatic mutation group [34 (13-68) years vs 55 (27-73) years, P=0.002]. The GATA2 germline/likely germline group had a significantly higher frequency of STAG2 mutations than the wild-type group [42.9% (6/14) vs 3.2% (41/1 296), P<0.001], whereas the somatic mutation group showed significantly higher frequencies of RUNX1 (21.3% vs 9.7%), BCOR (19.2% vs 5.9%), and SF3B1 (31.9% vs 10.6%) mutations (all P<0.05). Both GATA2 mutation groups had a significantly higher incidence of +8 karyotype than the wild-type group [germline/likely germline group: 35.7% (5/14) vs 14.2% (164/1 158), P=0.039; somatic mutation group: 26.1% (12/46) vs 14.2% (164/1 158), P=0.025]. ③ The proportion of patients with increased blasts (bone marrow blasts ≥5% or peripheral blood blasts ≥2% or presence of Auer rods) was significantly higher in the somatic mutation group than in the germline/likely germline group [74.5% (35/47) vs 21.4% (3/14), P<0.001]. ④ Among the patients with MDS aged <60 years, the somatic GATA2 mutation group had a significantly shorter median OS than the wild-type group[20 (95% CI: 12-27) months vs not reached, P=0.005]. Multivariate analysis revealed that GATA2 somatic mutation was an independent poor prognostic factor beyond the IPSS-M scoring system in patients with MDS aged <60 years (HR=2.43, 95% CI: 1.27-4.65, P=0.007) . Conclusion: Patients with germline and somatic GATA2 mutations exhibit distinct molecular and clinical profiles. GATA2 somatic mutation is an independent poor prognostic factor in patients with MDS aged <60 years.