Underexpression of EZH2 in Myelodysplastic Syndromes

Results: We found that 47% (n=37) of our samples have reduced EZH2 mRNA expression (less than half that of controls), but these data not statistically significant (p=0.159). Further analyses revealed that EZH2 is significantly underexpressed in MDS cases with chromosome 7 or 7q deletion (mean=0.4 fold, p=0.006). These deletions were also associated with lower EZH2 expression than was seen in diploid cells and cells with other cytogenetic abnormalities (p=0.041). To understand the effects of EZH2 expression alteration specifically, we performed survival analysis. Multivariate analysis indicated that, in contrast to previous findings, EZH2 underexpression is associated with better overall survival (OS) (p=0.012). We also examined treatments in our patient cohort and found that 61% of patients (n=53) received hypomethylating agents (HMA). In the HMA treatment cohort, non-responding patients (n=27) had lower EZH2 expression than responders (n=26), but that effect was not significant (p=0.12). However, in HMA responders, EZH2 expression was significantly lower in patients who achieved longer responses (more than 12 months, n=15) than in those who progressed or relapsed within 12 months (p=0.02).