Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults in Western world. Disease may have aggressive or indolent clinical course. Standard treatment is based on chemoimmunotherapy, such as FCR scheme, which consists of fludarabine, cyclophosphamide and rituximab. New treatment options include targeted therapy with ibrutinib and idelalisib, which inhibit B-cell receptor (BCR) signaling. The prostaglandin EP4 receptor represents a new potential target for the treatment of B cell leukemias and lymphomas. In this master thesis we evaluated selective EP4 receptor agonists L-902,688 and PgE1-OH. With use of cell viability assay and flow cytometry we demonstrated that they possess cytotoxic effects on CLL cells and act in a time and concentration dependent manner. Applying selective EP4 receptor antagonist CJ-042794 we confirmed that agonists exert their effects through EP4 receptor. EC50 values for L-902,688 and PgE1-OH were significantly lower on CLL cells as compared to lymphoblastoid cell lines (LCL) and peripheral blood mononuclear cells (PBMC), which confirms their selectivity towards malignant B lymphocytes. We also evaluated the most commonly used drug for CLL fludarabine and novel targeted drugs ibrutinib and idelalsib. After 24 h EC50 values for fludarabine were significantly higher as compared to L-902,688 and PgE1-OH and IC50 values for idelalisib were significantly higher only when compared to L-902,688. After 48 h EC50 (IC50) values for fludarabine, ibrutinib and idelalisib were 4,65 μM, 3,15 μM and 8,84 μM, respectively, and were comparable to EC50 for L-902,688 and PgE1-OH. Clinical outcome of therapy is often improved when combining drugs with different mechanism of action, therefore we have decided to evaluate potential synergism of L-902,688 and PgE1-OH with fludarabine, ibrutinib and idelalisib. Combining EP4 receptor agonists with fludarabine and ibrutinib proved to have synergistic outcome at lower concentrations of drugs, whereas idelalisib, which is the least cytotoxic among tested drugs (IC50 was 20,64 after 24 h and 8,84 μM after 48 h), proved to exert synergy in all tested concentrations of drugs. Using annexin V we demonstrated that L-902,688 and PgE1-OH induce apoptosis in malignant B lymphocytes and with CFSE assay we have shown they are also cytostatic. Both compounds inhibited cell division after 48 h, which implies we could also inhibit proliferation of CLL cells in vivo. We have also shown that expression of EP4 receptor is not affected by this two drugs, which confirms the importance of the EP4 receptor as a potential therapeutic target. Selective EP4 receptor agonists exert both cytotoxic and cytostatic effects and synergistic effects are present when combined with novel therapeutics in vitro, therefore this could lead to new treatment options for CLL.