Higher expression levels are associated with worse overall and leukaemia-free survival in myelodysplastic syndrome patients.

mutations are frequently detected in various myeloid neoplasms and implicate unfavourable clinical outcomes in patients with myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). On the other hand, high expression of is also correlated with poor prognosis in AML patients. However, the clinical relevancy of expression in MDS patients remains elusive. This study aimed to investigate the prognostic and biologic impacts of expression in MDS patients. We recruited 341 MDS patients who had sufficient bone marrow samples for next-generation sequencing. Higher expression occurred more frequently in the patients with Revised International Prognostic Scoring System (IPSS-R) higher-risk MDS than the lower-risk group. It was closely associated with poor-risk cytogenetics and mutations in , , , , , and . Furthermore, patients with higher expression had significantly shorter leukaemia-free survival (LFS) and overall survival (OS) than those with lower expression. Subgroups analysis revealed that higher- group consistently had shorter LFS and OS than the lower- group, no matter was mutated or not. The same findings were observed in IPSS-R subgroups. In multivariable analysis, higher expression appeared as an independent adverse risk factor for survival. The prognostic significance of expression was validated in two external public cohorts, GSE 114922 and GSE15061. In summary, we present the characteristics and prognosis of MDS patients with various expressions and propose that expression complement mutation in MDS prognostication, wherein patients with wild but high expression may need more proactive treatment.