EZH2, new diagnosis and prognosis marker in acute myeloid leukemia patients

Abstract Purpose Acute myeloid leukemia (AML) is a heterogeneous disease. The discovery of novel discriminative biomarkers remains of utmost value for improving outcome predictions. Enhancer of zeste homolog 2 ( EZH2 ) is a histone methyltransferase of H3K27me3. It is frequently up-regulated in human cancers and associated with silencing of differentiation genes. We aimed herein to investigate the prevalence and prognosis impact of somatic EZH2 mutations and their potential associations with other prognostic markers FLT3 , NPM1 , DNMT3A and IDH2 . Materials and methods Our study population was composed of 211 Tunisian patients with de novo AML and 14 healthy donors. The 11 last exons coding the set domain of EZH2 were investigated by PCR and Sanger sequencing. Results EZH2 mutations were identified in 66/211 (31%) patients with a sex ratio of 1.06. The presence of EZH2 mutations was statistically significantly associated with failure consolidation therapy (p = 0.004). There were no differences in the incidence of EZH2 mutations and FLT3 -ITD, NPM1 , DNMT3A and IDH2 mutations. When EZH2 mutations were associated with those of FLT3 or IDH2 , a short duration of progression free survival was observed (p  EZH2 mutated patients (p  Conclusions Given these data we conclude that EZH2 mutations are frequent in our patients, and can be used as a prognosis marker in combination with FLT3 , IDH2 mutations and CD7 marker, to stratify AML patients and to guide therapeutic decisions.