Anti-Tumour Effect of Zoledronate in Cells from B Chronic Lymphoytic Leukemia and Low-Grade Lymphoma Patients.

Recent studies demonstrate that bisphosphonates - anti-resorptive drugs - have direct anti-tumour effect in many tumour cell lines, including hematopoietic ones. The aim of this study was to evaluate the apoptotic effect of Zoledronate in cells from B chronic lymphocytic leukemia (B-CLL) and low-grade lymphoma (LGL) patients. Samples of 19 B-CLL or LGL patients were incubated with Zoledronate 100 μM in RPMI medium supplemented with fetal bovine serum 10% at 37⁰C for 12h. Apoptosis using Annexin V assay, by flow cytometry (FC), was observed in 8 out of 19 (42,1%) patients despite previous treatment. Multidrug resistance (MDR) phenotype was performed using rhodamine-123 efflux assay by FC. Our results demonstrate that Zoledronate 100 m M can induce apoptosis in B malignant lymphocytes despite previous treatment and MDR phenotype. So, patients previously treated with distinct therapeutic agents or not can potentially benefit from the anti-tumour effect of Zoledronate. This is the first work demonstrating the anti-tumour effect of Zoledronate in newly obtained cells from patients with B-CLL and LGL. These results in association with evidences from recent studies suggest that Zoledronate may have an important and complementary role in hematological malignant diseases.