Integrating EVI1 expression into prognostic models for MDS: Insights from IPSS-R and IPSS-m subgroup analyses

Abstract

Abstract Background: EVI1 is frequently overexpressed in acute myeloid leukemia (AML) and associated with poor prognosis. Although MDS patients with 3q26 rearrangements often show EVI1 overexpression and are prone to progression to AML, the clinical significance of EVI1 expression in MDS remains unclear. Aims To evaluate the clinical and prognostic relevance of EVI1 expression in patients with MDS. Methods We retrospectively analyzed 522 MDS patients who had not received prior therapy between January 2023 and December 2024. EVI1 expression was quantified by qPCR, with high-expression defined as EVI1/ABL ≥8.0%. Patients were stratified using IPSS-R and IPSS-M scores. Clinical features, immunophenotypes, mutational profiles (in 100 patients with NGS data), and survival outcomes (in 168 patients with follow-up data) were compared between EVI1-high and EVI1-low groups. Results Among 522 patients, 260 (49.8%) showed EVI1 high expression. These patients had a higher percentage of bone marrow blasts, elevated WT1 and PRAME expression, and were more often categorized as intermediate/high risk by IPSS-R. Flow cytometry showed enrichment of aberrant immature myeloid phenotypes (CD34⁺CD117⁺CD33⁺CD38⁺) in the EVI1-high group, whereas the EVI1-low group more frequently exhibited aberrant erythroid features (CD36⁺CD105⁺). EVI1 expression was significantly higher in patients with 3q26 rearrangements compared to those without (105.0% vs. 17.1%, p<0.0001). SETBP1 mutation was more frequent in the EVI1-high group (8.0% vs. 0.0%, p=0.002). EVI1 overexpression was associated with inferior overall survival (OS) and event-free survival (EFS) (p=0.003 and p=0.025, respectively). Multivariate Cox analysis identified EVI1 expression and age as independent predictors of OS. In IPSS-R low-risk patients, EVI1 overexpression predicted worse EFS (p=0.037), but had no impact in intermediate/high-risk patients. Using IPSS-M, no patients fell into the very low-risk category, and 88% were classified as moderate-high to very high risk. Within each IPSS-M subgroup, EVI1 expression was not significantly associated with survival outcomes. Summary/Conclusion EVI1 overexpression defines a biologically and clinically distinct high-risk MDS subgroup, associated with adverse outcomes, especially in IPSS-R low-risk patients. EVI1 may serve as an independent prognostic biomarker. In patients with NGS data, IPSS-M provided robust risk stratification, and EVI1 expression had no additional prognostic impact within IPSS-M subgroups.