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The aim of this study was to investigate the in vitro immunomodulatory effects of zoledronic acid (Zol) on peripheral blood V?9/Vd2 (?d) T cells of normal donors and multiple myeloma (MM) patients.?dT cells were stimulated with Zol and low doses of interleukin-2 (IL-2), and then analyzed for proliferation, cytokine production, and generation of effector activity against myeloma cell lines and primary myeloma cells. Proliferation of?dT cells was observed in 100%of normal donors and 50%of MM patients.?dT cells produced IFN-?, surface mobilized the CD107a and CD107b antigens, and exerted direct cell-to-cell antimyeloma activity irrespective of the ability to proliferate to Zol and IL-2. The memory phenotype was predominant in the MM?dT cells that proliferated in response to Zol (responders), whereas effector cells were predominant in those that did not (nonresponders). Zol induced antimyeloma activity through the monocyte-dependent activation of?dT cells and by enhancing the immunosensitivity of myeloma cells to?dT cells. Mevastatin, a specific inhibitor of hydroxy-methylglutaryl-CoA reductase, completely abrogated this antimyeloma activity.Leukemia (2005) 19, 664-670. doi:10.1038/sj.leu.2403693 Published online 3 March 2005 [ABSTRACT FROM AUTHOR]

Chronic Myeloid Leukemia (CML) has always been an ideal model to understand the molecular pathogenesis of human leukaemias and the way to cure them. This can be ascribed to the fact that CML was the first human cancer demonstrated to be strongly associated to the presence of a recurrent chromosomal translocation (the t(9;22)(q34;q11) that creates the Philadelphia (Ph)-chromosome) and to a specific molecular defect, the formation of a hybrid BCR-ABL gene that generates new fusion proteins endowed with a constitutive tyrosine-kinase (TK) activity, strongly implicated in the pathogenesis of the disease. The introduction into clinical practice of imatinib, (Glivec, Gleevec, Novartis), a potent tyrosine kinase inhibitor of the Bcr-Abl protein as well as of a restricted number of other TKs, has not only produced a substantial improvement in the treatment of CML, but represents a major break-through in the perspective of opening a new era, that of molecularly targeted therapy, in the management of other types of leukemia, lymphoma and cancer in general.