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

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.

Prognostic Significance of Long Non Coding RNA ANRIL and SNHG14 in Acute Myeloid Leukemia.

BACKGROUND: Long non-coding RNAs (lnRNAs) play a pivotal role in various malignancies including AML. Therefore, we decided to study both lnRNA ANRIL and lnRNA SNHG14 gene expressions in patients with AML to better understand their role in AML risk development, clinical presentation, and prognosis. METHODS: The current prospective study included two hundred participants, 100 AML patients and 100 control subjects. Bone marrow analysis was made to all patients, in addition to gene expression molecular testing of both lnRNA ANRIL and lnRNA SNHG14. RESULTS: Both lnRNA SNHG14 and lnRNA ANRIL showed high expression levels in AML bone marrow samples compared to non-AML subjects and were remarkably associated with lower Complete Remission (OR: 3.449, 95% CI: 1.324-8.985, p=0.011 for ANRIL and OR: 3.955, 95% CI: 1.510-10.356, p=0.005 for SNHG14), Relapse Free Survival (HR=3.504, 95%CI: 1.662-7.387, p=0.001 for ANRIL and HR=4.094, 95%CI: 1.849-9.067, p=0.001 for SNHG14) and Overall Survival (HR=3.353, 95%CI: 1.434-7.839, p=0.005 for ANRIL and HR=3.094, 95%CI: 1.277-7.494, p=0.012 for SNHG14), favouring poor prognostic significance in AML. CONCLUSION: This suggests that both lnRNA ANRIL and lnRNA SNHG14 could be used in the future as prognostic biomarkers to help in treatment decisions and follow up of AML patients.