Coupling of early response gene expression to distinct regulatory pathways during alpha-interferon and phorbol ester-induced plasmacytoid differentiation of B chronic lymphocytic leukaemia cells.
Phorbol esters (phorbol 12-myristate 13-acetate; PMA) and alpha-interferon (alpha-IFN) act through divergent signal transduction pathways to induce B chronic lymphocytic leukaemia cells (B-CLL) to undergo plasmacytoid differentiation in vitro. By using a panel of PMA-inducible early response gene probes we show that these two different effectors are coupled to second messenger pathways that do not converge on a common gene regulatory programme in differentiation of B-CLL cells. Moreover, using the calcium ionophore, A23187, four distinct regulatory classes of early response gene could be defined implying that multiple regulatory pathways may mediate the process of terminal differentiation in B lymphocytes.
Murphy
J J
JJ
Dept. of Haematology, Royal Free Hospital Medical School, Hampstead, London, UK.
Norton
J D
JD
D001402:B-Lymphocytes / Q000187:drug effects*; D015152:Blotting, Northern; D000001:Calcimycin / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D005809:Genes, Regulator / Q000187:drug effects; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000378:metabolism; D010703:Phorbol Esters / Q000494:pharmacology*; D010950:Plasma Cells / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D015290:Second Messenger Systems / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects
D007370:Interferon Type I; D010703:Phorbol Esters; D012333:RNA, Messenger; D000001:Calcimycin