Relationship between HLA-DR expression by normal myeloid progenitor cells and inhibition of colony growth by prostaglandin E. Implications for prostaglandin E resistance in chronic myeloid leukemia.
The expression of HLA-DR antigens by normal myeloid progenitor cells (CFU-GM) has been linked to inhibition of colony growth by prostaglandin E (PGE), while resistance to the inhibitory effects of PGE in chronic myeloid leukemia (CML) has been attributed to a lower fraction of HLA-DR+ CFU-GM in this disease. However, we have previously shown that virtually all CFU-GM in normal bone marrow (NBM) as well as CML peripheral blood express HLA-DR antigens, which raises the possibility that these surface molecules may not be the sole determinants of a progenitor cell's sensitivity to PGE. In order to evaluate the relationship between HLA-DR expression and prostaglandin inhibition, we partially purified NBM progenitor cells using fluorescence-activated cell sorting to prepare cell fractions with high and low HLA-DR antigen density. Normal progenitor cells with high DR density tended to form monocyte colonies in agar culture, whereas the low DR density fraction was enriched for granulocyte colony-forming cells. Inhibition by PGE was greatest in the high DR+ fraction and was largely restricted to monocyte progenitor cells. Inhibition of CFU-GM by PGE was less in CML than in NBM, but this decreased inhibition correlated with a significantly lower number of monocyte-CFU in CML. These data suggest that high HLA-DR antigen density may select for normal progenitor cells that are committed to monocyte differentiation and are, therefore, more likely to be inhibited by PGE. The relative deficit of monocyte progenitor cells in CML may partially explain the phenomenon of PGE resistance in this disease.
Cannistra
S A
SA
Herrmann
F
F
Davis
R
R
Nichols
K
K
Griffin
J D
JD
D000527:Alprostadil / Q000494:pharmacology*; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D006098:Granulocytes / Q000145:classification / Q000166:cytology / Q000276:immunology; D006131:Growth Inhibitors / Q000494:pharmacology*; D006684:HLA-DR Antigens; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D006801:Humans; D007951:Leukemia, Myeloid / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000145:classification / Q000166:cytology / Q000276:immunology; D013535:Suspensions; D014410:Tumor Stem Cell Assay
D006131:Growth Inhibitors; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D013535:Suspensions; D000527:Alprostadil