T cell dysregulation and shift to T helper 2 responses, boosting tumor microenvironment support, contributes to the survival of leukemic B cells in Chronic Lymphocytic Leukemia. Interleukin (IL)-25 is involved in the initiation of T helper 2 cell responses. Signal transduction of IL-25 begins with the heterodimer receptor (IL-17RA/IL-17RB). The presence of IL-25 in the tumor microenvironment may affect the supportive effects of T cells in the surrounding tumor cell environment. The purpose of this study was to evaluate the role of IL-25 in the biology of CLL. IL-17RB expression in CD3+ and CD19+ cells was assessed in isolated peripheral blood mononuclear cells (PBMCs) of nine CLL patients and nine healthy subjects by real-time polymerase chain reaction and flow cytometry. B cells were positively enriched from PBMCs using magnetic-activated cell sorting (MACS). PBMCs and purified leukemic B cells were cultured with recombinant human IL-25 (20ng/ml) for 72 hours, then the viability and apoptosis of cultured cells were measured by MTT assay and AnnexinV/7AAD. Furthermore, the levels of CD69 expression on T lymphocytes and IL-17RB in T and B cells were determined by flow cytometry. The basal level of IL-17RB expression in CLL patients was significantly higher than that in control individuals. In addition, the percentage of IL-17RB+/CD3+, IL-17RB+/CD19+ cells and CD69+/CD3+ cells increased after 72 hours of culture with IL-25 in CLL patients compared to healthy subjects. IL-25 also reduces the apoptosis rate of tumor cells. We found that IL-25 could stimulate T cells in CLL patients and lower B cell death. This suggests that IL-25 might have a role in enhancing the survival of tumor cell by expressing receptors for inflammation, such as IL-17RB, and might be involved in the development of CLL.

Background and Objective: Peganum harmala is a medicinal plant that has been used for treatment of numerous diseases including viral, bacterial and parasitic infections. Anti-proliferative and anti-tumor effects of Peganum harmala extracts and its derivatives have been reported. In the present study, cytotoxic effect of Peganum harmala seeds aquaous extract on leukemic U937 and Molt-4 cells was evaluated in vitro. Materials and Methods: U937 and Molt-4 cells were cultured in RPMI with 10% FBS. Then, the cells at logarithmic growth phase were incubated with different concentrations of aquaous extract of Peganum harmala seeds (0. 1-5 mg/ml) for 24, 48 and 72 hours. Then, viability and proliferative response of leukemic cell lines was evaluated by trypan blue dye exclusion (TB) and MTT assays, respectively. Results: Peganum harmala aquaous extract has a cytotoxic effect on leukemic cells used in this study, dose and time-dependently. This cytotoxicity was shown at ≥ 0. 5 mg/ml after 24 hours and at ≥ 0. 1 mg/ml after 48 and 72 hours incubation time. The Peganum harmala seeds aqueous extract cytotoxicity at > 0. 2 mg/ml concentration was significantly increased with time in this order: 72 h>48 h>24 h. Conclusion: The leukemic cells used in this study showed sensitivity to Peganum harmala seeds aquaous extract dose and time dependently. This sensitivity significantly increased with time at > 0. 2 mg/ml concentration. Peganum harmala seeds aquaous extract shows cytotoxicity for leukemic cells and might be a valuable natural candidate in development of innovative therapeutic procedures for leukemia and probably other cancers.