Effects of la,25-Dihydroxyvitamin D3 on the Human Chronic Myelogenous Leukemia Cell Line RWLeu-41

The effects of la,25-dihydrox>vitamin D., (YD3) on proliferation, differentiation, and macromolecular synthesis in the new Philadelphia chromosome-positive chronic myelogenous leukemia cell line, RVVLeu4, were investigated. Binding of ['11]VI>, was saturable, with approxi mately 2000-3000 sites/cell, and half-maximal binding occurring at 0.210.33 nM. Treatment of R\VLeu-4 cells with VDj induced 24fl-hydroxylase activity, a marker of vitamin ]><responsiveness in many tissues. Exposure of RVVLeu-4cells to YD., also inhibited proliferation and DNA synthesis with a 50% effective dose of 3.5-10 nM within 72 h; in addition, protein and RNA synthesis »ereinhibited by VD.i treatment. Exposure of R\VLeu-4 cells to 5 nM VD3 for 72 h caused 50% of the cells to differentiate into macrophage/monocyte type cells as judged by nitroblue tetrazolium staining and adherence to plastic. Progressive expression of cell surface maturation-specific antigens of the monocyte/macrophage lineage was induced by treatment of R\VLeu-4 cells with YD., for 24 to 72 h at doses that inhibited cellular proliferation, c-myc RNA, which is constitutively expressed in R\YLeu-4 cells, increased after 0.5 h of treatment with 50 nM YD.,and then rapidly decreased to barely detectable levels after 4 h of treatment. Finally, the in vitro tyrosine kinase activity associated with the p210bcr"bloncogene product was decreased approxi mately 50% by YD., treatment. Because of the presence of a functional receptor-effector system for YD] and multiple biological responses to the hormone, these cells provide a unique model system with which to probe the specific effects of YD-, on cell growth and differentiation in chronic myelogenous leukemia.