Liposomal 1,25 (OH)(2) vitamin D-3 compounds block proliferation and induce differentiation in myelomonocytic leukaemia cells

The vitamin D-3 derived hormone 1,25 (OH)(2) vitamin D-3 (1,25 D-3) is able to induce growth arrest and differentiation in myelomonocytic leukaemic cells. In order to allow for specific delivery to leukaemic cells the lipophilic compound was incorporated into the lipid membranes of liposomes. Liposomal 1,25 D-3 reduced proliferation as measured by H-3-thymidine incorporation in HL60 leukaemia cells by up to 60%. When liposomes were prepared at different concentrations of 1,25 D-3 65% inhibition was achieved at 48 nM. The MC 1288 stereoisomer of 1,25 D-3 was more potent and had the same activity at 4.8 nM. The effect of the liposomal compounds was specific to myeloid cells as they reduced proliferation in myelomonocytic HL60, monoblastic U937 and monocytic Mono Mac 6 cells but not in the T-cell lines Jurkat and Molt 4. The antiproliferative effect of liposomal 1,25 D-3 was associated with an induction of differentiation sice treated HL60 cells showed a monocytic morphology, increased expression of CD14 and decreased expression of CD33. When peripheral blood leukaemic cells from M4 and M5 acute myeloid leukaemia (AML) patients were admixed with liposomal compounds an antiproliferative effect was sent in all five cases, including the two cases where free compounds led to enhanced growth. Liposomal delivery of 1,25 (OH)(2) vitamin D-3 may offer a novel approach to treatment of myelomonocytic leukaemia.