Down-regulation of CD5 mRNA in B-chronic lymphocytic leukemia cells by differentiation-inducing agents.
Most B chronic lymphocytic leukemia (CLL) cells express on their surface the CD5 antigen which is an activation marker on normal B cells. To investigate the control of CD5 expression in B-CLL cells, we examined several inducing agents for their effects on CD5 mRNA expression. Northern blot analysis demonstrated that the expression of CD5 mRNA could be up- or down-regulated depending on the inducers used. Treatment with direct activators of protein kinase C (PKC), the phorbol ester phorbol 12-myristate 13-acetate (PMA) or the natural agent bryostatin 1 (Bryo), caused increased CD5 mRNA expression after 8-16 h of incubation. In contrast, exposure to the dual signals of a PKC activator (PMA or Bryo) plus the calcium ionophore A23187 led to down-regulation of CD5 mRNA expression. The molecular alterations at the RNA level were accompanied by morphological changes: PMA and/or Bryo induced cellular features of activation while PMA plus A23187 or Bryo plus A23187 mediated morphological changes indicative of differentiation to plasmacytoid cells. The data suggest that as a consequence of maturation differentiated B-CLL cells down-regulate CD5 expression by analogy with the normal ontogenic process in which plasma cells, the end-stage cells of normal B cell differentiation, are CD5-.
Royal Free Hospital School of Medicine, Department of Haematology, London.
S M
SM
Gignac
M
M
Buschle
A V
AV
Hoffbrand
H G
HG
Drexler
D000368:Aged; D015703:Antigens, CD / Q000235:genetics*; D000943:Antigens, Differentiation / Q000235:genetics*; D054713:Bryostatins; D018956:CD5 Antigens; D000001:Calcimycin / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007783:Lactones / Q000494:pharmacology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology*; D018942:Macrolides; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000943:Antigens, Differentiation; D054713:Bryostatins; D018956:CD5 Antigens; D007783:Lactones; D018942:Macrolides; D012333:RNA, Messenger; D000001:Calcimycin; C046785:bryostatin 1; D013755:Tetradecanoylphorbol Acetate