Vitamin D3-driven signals for myeloid cell differentiation--implications for differentiation therapy

Primitive myeloid leukemic cell lines can be driven to differentiate to monocyte-like cells by 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), and, therefore, 1,25(OH)(2)D(3) may be useful in differentiation therapy of myeloid leukemia and myelodysplastic syndromes (MDS). Recent studies have provided important insights into the mechanism of 1,25(OH)(2)D(3)-stimulated differentiation. For myeloid progenitors to complete monocytic differentiation a complex network of intracellular signals has to be activated and/or inactivated in a precise temporal and spatial pattern. 1,25(OH)(2)D(3) achieves this change to the 'signaling landscape' by (i) direct genomic modulation of the level of expression of key regulators of cell signaling and differentiation pathways, and (ii) activation of intracellular signaling pathways. An improved understanding of the mode of action of 1,25(OH)(2)D(3) is facilitating the development of new therapeutic regimens.