Monocytic differentiation induction of HL-60 cells by MC 903, a novel vitamin D analogue.
1.25 (OH)2D3 is a potent inducer of differentiation of leukaemic cells into a monocytic direction. However, therapeutic application is difficult because of the development of hypercalcaemia. We examined a novel vitamin D analogue, MC 903, which is at least 100 times less effective on calcium metabolism in rats than 1.25 (OH)2D3. Using the HL-60 cell line, differentiation was measured with a comprehensive panel of qualitative and quantitative parameters. Development of monocytic cells was shown morphologically, immunophenotypically and functionally by increased capability of reducing NBT (vs cultures without MC 903, p less than 0.0001) and by qualitatively and quantitatively increased non-specific esterase activity. Furthermore, a concomitant decreased activity of myeloperoxidase and lactate dehydrogenase was noticed. In conclusion, MC 903 is a potent inducer of monocytic differentiation, comparable with 1.25 (OH)2D3 and will therefore be an interesting and potential therapeutic agent for studies in human acute leukaemia.
Rebel
V I
VI
Department of Haematology, Free University Hospital, Amsterdam, The Netherlands.
Ossenkoppele
G J
GJ
van de Loosdrecht
A A
AA
Wijermans
P W
PW
Beelen
R H
RH
Langenhuijsen
M M
MM
D000208:Acute Disease; D015703:Antigens, CD / Q000032:analysis; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002265:Carboxylic Ester Hydrolases / Q000032:analysis; D002453:Cell Cycle; D002454:Cell Differentiation / Q000187:drug effects*; D006801:Humans; D007951:Leukemia, Myeloid / Q000276:immunology / Q000473:pathology*; D009000:Monocytes / Q000276:immunology / Q000473:pathology* / Q000648:ultrastructure; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; C055085:calcipotriene; D002265:Carboxylic Ester Hydrolases; C021855:naphthylbutyrate esterase; D002117:Calcitriol