Epigenetically targeted therapy potentially represents a novel way of treating hematologic malignancies, including diffuse large B-cell lymphoma (DLBCL), especially those cases resistant to standard therapeutic options and in patients with relapsed disease. As shown in this thesis, histone deacetylase inhibitors (HDACi) and hypomethylating agents yield synergistic effect in growth inhibition of malignant DLBCL cells. This effect has been demonstrated in in vitro analysis of cell viability, apoptosis induction, caspase system activation and histone acetylation in permanent and primary DLBCL lines utilizing the relative risk ration (RRR) calculations. Efficacy of decitabine and panobinostat (LBH589) in malignant cell growth inhibition has also been confirmed in in vivo human lymphoma xenograft model with a significant statistical difference (p < 0.05) in the mean tumour volume located on the flank of the animal in the group that received combination of decitabine and panobinostat compared to the single drug groups or the one that received vector only. Genome wide methylation analysis and gene expression profiling has been used to determine mechanistic and molecular basis for the synergistic effect of this combination. These analyses identified three potential tumour suppressors, TP73, MXD4 and CAV1, the synthesis of which was reactivated in cells treated with panobinostat and decitabine. Findings from this thesis are a part of a wider analysis in an effort to establish a pharmacology/biology systems model within B-cell neoplasm context. Practically, it will be a foundation for a clinical trial exploring efficacy of epigenetically targeted therapy.