Cell-type-specific early response gene expression during plasmacytoid differentiation of human B lymphocytic leukemia cells.
Monoclonal B lymphocytes from B cell chronic lymphocytic leukemia (B-CLL) can be induced to undergo plasmacytoid differentiation in vitro by the phorbol ester, phorbol 12-myristate 13-acetate (PMA). By differential screening of a cDNA library derived from cells treated with phorbol ester we have isolated and characterised a set of early response genes (ERGs) displaying rapid transient up-regulation of expression in response to PMA. Cross-hybridisation studies showed that PMA probably induces the expression of over one hundred distinct genes, implying an ERG complexity comparable to that activated by mitogenic stimulation of fibroblasts and normal T lymphocytes. Of 13 genes analysed in detail, most were induced by PMA without a requirement for de novo protein synthesis, whilst nuclear run-on analysis showed that at least some of the more abundant classes of ERG were up-regulated through transcriptional mechanisms. In a proliferating variant B-CLL population, few differences in ERG expression were seen, suggesting that these genes are part of a gene regulatory pathway coupled to the differentiative rather than the proliferative response of B-CLL cells. However, studies in a range of cell types revealed a surprisingly diverse pattern of PMA-induced expression where most ERGs were relatively B-CLL-specific. This implies an extreme diversity of gene regulatory pathways activated in the primary response by phorbol ester generally and suggests that the onset of PMA-induced plasmacytoid differentiation of B-CLL cells is preceded by activation of a complex gene regulatory program that is largely unique to this maturation-arrested B cell.
Murphy
J J
JJ
Department of Haematology, Royal Free Hospital School of Medicine, London, U.K.
Norton
J D
JD
D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D001483:Base Sequence; D002454:Cell Differentiation; D003001:Cloning, Molecular; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007700:Kinetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000235:genetics*; D008969:Molecular Sequence Data; D010950:Plasma Cells / Q000378:metabolism / Q000473:pathology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000235:genetics
D013755:Tetradecanoylphorbol Acetate