Induction of macrophage differentiation of human normal and leukemic myeloid stem cells by 1,25-dihydroxyvitamin D3 and its fluorinated analogues
Koeffler, H.P.; Amatruda, T.; Ikekawa, N.; Kobayashi, Y.; Deluca, H.F.
Cancer Research 44(12 Pt 1): 5624-5628
1984
ISSN/ISBN: 0008-5472 PMID: 6594194 Document Number: 221692
1,25-dihyroxyvitamin D3 [1,25-(OH)2D3] and 2 fluorinated analogs [24,24-F2-1,25-(OH)2D3 and 26, 26, 26, 27, 27, 27-F6-1,25-(OH)2D3] were found to induce macrophage differentiation of human normal and leukemic myeloid stem cells. The addition of either 1,25-(OH)2D3 or 1 of the 2 fluorinated analogs at concentrations as low as 10-9 M to culture plates containing normal human marrow cells stimulated myeloid stem cells to preferentially differentiate to colonies of monocytes and macrophages. Over 80% of the normal human myeloid colonies were composed of only monocytes and macrophages in culture plates containing 10-7 M 1,25-(OH)2D3 or 1 of the fluorinated analogs. In contrast, control plate not containing 1,25-(OH)2D3 had < 35% macrophage colonies. Likewise, 1,25-(OH)2D3 and the 2 vitamin D analogs induced macrophage differentiation of leukemic colony-forming cells taken from patients. In plates containing 10-7 M 1,25-(OH)2D3 or 1 of the analogs at 10-8, 80% of chronic myelogenous leukemia and .apprx. 50% of acute nonlymphocytic leukemia colony-forming cells differentiated to macrophage-like cells. Control plates had about 30 and 20% macrophage colonies in cultures from chronic myelogenous leukemia and acute nonlymphocytic leukemia patients, respectively. It was suggested that 1,25-(OH)2D3 may play a role in hematopoiesis. The compound or a related analog may possibly have a therapeutic role in some leukemias.