1 alpha-Hydroxyvitamin D3 in the treatment of primary myelofibrosis: in vitro effect of vitamin D3 metabolites on the bone marrow fibroblasts.
Thrombocytopenia and splenomegaly improved in one of the four patients receiving 1 alpha-hydroxyvitamin D3 (1 alpha(OH)D3) for treatment of primary myelofibrosis (PMF). We compared the clinical results with the in vitro effects of vitamin D3 metabolites on the growth and collagen synthesis of bone marrow fibroblasts. The effects of vitamin D3 metabolites on control human bone marrow fibroblasts were first studied in vitro. On the growth, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) inhibited the platelet derived growth factor (PDGF) or human serum-induced proliferation at the concentrations of more than 10(-10) M, while in the presence of transforming growth factor-beta (TGF-beta) the inhibitory effects were mild or non-inhibitory. Both vitamin D3 metabolites inhibited procollagen synthesis at a concentration of more than 10(-8) M. The effect of 1,25(OH)2D3 on the PMF patients was examined. In two of the four patients, the human serum-induced growth inhibitory effect was observed at the concentration of 10(-8) M, in one patient no inhibition was observed and in one patient inhibition was observed at 10(-10) M, as was observed in the control donors. During the treatment with 1 alpha(OH)D3 the serum level of 1,25(OH)2D3 was 1-2 x 10(-10) M. These findings suggest that a minority of PMF patients have marrow fibroblasts with growth sensitivity to a pharmacological level of vitamin D3 and could be treated with 1 alpha(OH)D3 with some clinical improvements.
Department of Internal Medicine, Hiroshima University, Japan.
H
H
Hyodo
A
A
Kimura
Y
Y
Nakata
H
H
Ohta
A
A
Kuramoto
D000368:Aged; D001853:Bone Marrow / Q000187:drug effects*; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D006887:Hydroxycholecalciferols / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D055728:Primary Myelofibrosis / Q000188:drug therapy*
D006887:Hydroxycholecalciferols; D002762:Cholecalciferol; C008088:alfacalcidol