Expression of Enhancer of Zeste Homolog 2 (EZH2) Gene in Acute Myeloid Leukemia

Abstract

Background: Enhancer of Zeste Homolog 2 (EZH2) is the catalytic subunit of the chromatin modifying enzyme polycomb repressive complex 2 (PRC2). As a complex, these proteins selectively silence target genes through trimethylation of histone 3 at lysine 27. EZH2 is strongly oncogenic. It has been observed in various malignancies which makes it an interesting therapeutic target. Whether it functions as a tumor suppressor or oncogene in acute leukemia is not settled. Aim of this work: This study aimed at determining the expression levels of EZH2 gene in a cohort of adult Egyptian patients newly diagnosed with acute myeloid leukemia (AML). Materials and methods: The present study included 45 de novo AML patients and 40 healthy subjects of matched age and sex as a control group. All study participants were subjected to complete blood count (CBC), bone marrow examination, immunophenotyping, conventional cytogenetic studies and Detection of EZH2 gene expression levels by real time quantitative polymerase chain reaction (RQ-PCR). Results: EZH2 was significantly downregulated in AML patients compared to controls (p<0.001). There was no significant difference in EZH2 level when considering age, sex, bone marrow blasts count, cytogenetic studies, type or site of infection. Low EZH2 expression was associated with higher mortality (31 patients, 68.9%). Conclusions: Low EZH2 expression is prevalent in Egyptian AML patients subsequently; it is suggested to function as tumor suppressor gene rather than an oncogene. Moreover, EZH2 downregulation is associated with resistance to chemotherapy and high mortality rate.