Nevene Ramsis
Canal University Medical School, Egypt
Title: Assessment of CCAAT/enhancer binding protein α gene methylation in acute myeloid leukemia patients in Egypt: relation to response to induction therapy
Biography
Biography: Nevene Ramsis
Abstract
Background: Global gene promoter studies, as well as gene-specific approaches, have revealed that aberrant promoter methylation is a common event in AML. One such gene, CCAAT/enhancer binding protein α (C/EBP α), is a key transcription factor involved in the regulation of cell proliferation and differentiation in a variety of cell types, particularly in the hematopoietic system. Because of the pharmacologic reversibility of epigenetic changes by drugs, such as the DNA-demethylating agent, epigenetic therapy seems prominently among novel leukemia treatment strategies. Purpose: The present work is a cohort study that aimed at assessing the frequency of promoter methylation of the CEBP α gene in 70 cytogenetically normal, newly diagnosed AML Egyptian patients. Furthermore, the relation between the methylation status of the CEBP α gene and the outcome of standard induction therapy on day 28 was evaluated. Patients and methods: purified genomic DNA samples from the 70 newly diagnosed AML patients were subjected to bisulfate modification before methylation-specific polymerase chain reaction was performed to assess the CEBP α gene methylation status. Clinical and laboratory assessment of patients after 28 days of induction of standard therapy was performed. Results and conclusion: fifty-four percent of AML samples showed CEBP α gene methylation at the promotor region. Positive methylation was seen associated with blast expression of T-cell markers and blast counts in peripheral and bone marrow samples; but did not privilege a particular FAB classification subtype or relate to age and gender. The positive CEBP α gene methylation status was seen acceptable to predict AML patients with resistant clone who did not respond to standard induction therapy and blast clearance at day 28 (95% CI: 0.466–0.985, p= 0.005). Assessment of CEBP α gene methylation in AML patients might lead to refined prognostic stratification and suggest differentially tailored treatment based on its methylation status.