<em>E-Cadherin</em> and <em>MMP-9</em> Gene Promoter Methylation in CLL Pathogenesis and Prognosis

Background/Objectives: Chronic lymphocytic leukemia (CLL) is characterized by genetic and epigenetic alterations. This study aimed to assess the methylation status of E-Cadherin and MMP-9 gene promoters and to explore their relationships with disease pathogenesis and hematological parameters in CLL patients. Methods: A case–control study was conducted including 70 newly diagnosed CLL patients and 70 age- and sex-matched healthy controls. Promoter methylation of E-Cadherin and MMP-9 genes was evaluated using methylation-specific PCR (MSP) and methylation-sensitive restriction enzyme PCR (MSRE-PCR), respectively. Results: The median patient age was 62 years, and 68.5 % were males. Binet stage A was the most common (57.3 %). E-Cadherin promoter methylation was detected in 75.7 % of CLL patients and 77.1 % of controls (p = 0.91), showing no significant association with disease occurrence, however, it showed a significant correlation with higher lymphocyte counts (p = 0.01). In contrast, MMP-9 promoter methylation was significantly less frequent in CLL cases (70.0 %) than in controls (100 %, p = 0.001). Unmethylated MMP-9 correlated significantly with female gender (p = 0.02), lower hemoglobin (p = 0.031), and reduced platelet counts (p = 0.001) and higher lymphocytes counts (p = 0.035). Conclusion: MMP-9 promoter hypomethylation may play a pathogenic role in CLL and is associated with female gender and cytopenia, whereas E-Cadherin methylation appears non-specific. MMP-9 methylation status could therefore serve as a potential biomarker for CLL biology and prognosis.