Epigenetic silencing of the DAPK1 gene in Egyptian patients with chronic myeloid Leukemia

Abstract

BackgroundEpigenetics play a crucial role in the carcinogenesis of hematological malignancies. Alterations of the methylation status in the promoter region of tumor suppressor genes, such as DAPK1, cause loss of gene function and subsequent progression of Chronic Myelogenous Leukemia (CML) to more advanced stages. This study aimed to analyze the methylation status of the DAPK1 gene promoter in different phases of CML patients. Material and methodsThe study included 200 CML patients positive for BCR/ABL and 50 as control. Clinicopathological examination was done for all patients. DAPK1 gene methylation was determined by the Methylation Specific-PCR method. ResultsDAPK1 promoter methylation was evident in 37.0% of CML patients and it was more frequent in affected females than males (p = 0.014). Platelet count and bone marrow blast cells were significantly different in the methylated group compared to the unmethylated group (p = 0.001 and p = 0.034 respectively). Out of the methylated group, fifteen patients had a hemimethylated pattern. Unmethylation was more frequent in patients in the chronic phase (66.5%; p = 0.001). In contrast, methylation was found in 75.0% of patients in the accelerated phase (p = 0.040) with an odds ratio (OR) of 5.470 (95% CI: 1.074–27.849). Similarly, methylation was found in 85.7% of patients in the blast phase (p = 0.027) where the OR increased to 11.029 (95% CI: 1.300–93.513). By logistic regression analysis, there was significant association between methylation pattern and CML disease clinical outcome. ConclusionCML progression is closely associated with methylation changes in the DAPK1 promoter region. Identification of the underlying epigenetic mechanisms in CML is valuable in predicting disease prognosis and offering suitable management for each patient.