Functional significance of induction of differentiation in human myeloid leukaemic blasts by 1,25-dihydroxyvitamin D3 and GM-CSF.
We studied the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and granulocyte-macrophage colony stimulating factor (GM-CSF) on monocytic differentiation of the U937 leukaemic cell line and blasts from patients with AML. 1,25(OH)2D3 and GM-CSF synergistically increased functional and phenotypic aspects of differentiation in the U937 cell line. In addition, the effective concentration of 1,25(OH)2D3 was reduced by up to 100 times in the presence of GM-CSF. GM-CSF alone had little differentiation-inducing effect on AML blasts. 1,25(OH)2D3 induced CD14 antigen expression in 67% AML blast populations and increased functional activation in 36%. 1,25(OH)2D3 and GM-CSF in combination cooperated to further induce CD14 antigen expression in one third of blast populations, while having no further effect on function. Failure to induce functionally effective levels of FcRII antigen on AML blasts following stimulation with 1,25(OH)2D3 and GM-CSF may account for the lack of functional activation.
Kelsey
S M
SM
Department of Haematology, London Hospital Medical College, U.K.
Makin
H L
HL
Newland
A C
AC
D000208:Acute Disease; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007951:Leukemia, Myeloid / Q000473:pathology*; D018950:Lipopolysaccharide Receptors; D009000:Monocytes / Q000166:cytology* / Q000276:immunology / Q000473:pathology; D010587:Phagocytosis; D010641:Phenotype; D017452:Receptors, IgG; D011990:Receptors, Transferrin / Q000378:metabolism; D016897:Respiratory Burst; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D011990:Receptors, Transferrin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002117:Calcitriol