Farnesyltransferase inhibitors: molecular evidence of therapeutic efficacy in acute lymphoblastic leukemia through cyclin D1 inhibition.

BACKGROUND Farnesyltransferase inhibitors have the ability to interfere with various intracellular pathways, reducing cell survival and proliferation. They have become an attractive tool for cancer therapy, namely acute leukemias. In this work, we have studied the efficacy of α-hydroxyfarnesylphosphonic acid (α-HFPA) in CEM (acute T-cell lymphoblastic leukemia) in culture. MATERIALS AND METHODS CEM cells were incubated with α-HFPA at different concentrations; viability and proliferation studies were performed using the trypan blue exclusion assay and cell morphological analysis. Expression of lamin A/C, cyclin D1 and BAD were analyzed by flow cytometry. RESULTS Our results show that α-HFPA significantly decreases Farnesyltransferase activity, reduces cell proliferation and induces cell death through apoptosis in CEM cells, which is correlated with a reduction of cyclin D1 levels. CONCLUSION This study suggests that α-HFPA blocks the cell cycle and induces cell death through apoptosis in CEM cells and may be a therapeutic approach in ALL.