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National Institute of Environmental Health Sciences

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Publication Detail

Title: Constitutive and activation-inducible cyclooxygenase-2 expression enhances survival of chronic lymphocytic leukemia B cells.

Authors: Ryan, Elizabeth P; Pollock, Stephen J; Kaur, Kuljeet; Felgar, Raymond E; Bernstein, Steven H; Chiorazzi, Nicholas; Phipps, Richard P

Published In Clin Immunol, (2006 Jul)

Abstract: We recently reported that activated normal human B lymphocytes express Cox-2. These findings prompted us to evaluate whether human B-CLL cells express Cox-2 and synthesize prostaglandins. In contrast to naive human B cells, B-CLL cells constitutively expressed Cox-2 protein and produced PGE2, PGF2alpha, and TXA2. Elevated Cox-2 expression was seen in a subgroup of B-CLL cells that exhibit poor prognostic factors, including unmutated variable heavy chain status and increased CD38 expression. Furthermore, stimulation of B-CLL cells with CD40 ligand plus TNFalpha increased Cox-2 levels. The role of Cox-2 in promoting B-CLL survival was investigated using nonselective and selective Cox-2 inhibitors. Significant reductions in B-CLL survival occurred following Cox-2 inhibition. These new findings support that constitutive Cox-2 expression in B-CLL cells promotes their survival and possibly their expansion in vivo. It will therefore be important to evaluate drugs that inhibit Cox-2 as potential therapeutic agents in B-CLL in vivo.

PubMed ID: 16473553 Exiting the NIEHS site

MeSH Terms: B-Lymphocytes/cytology; B-Lymphocytes/enzymology*; B-Lymphocytes/immunology; Cell Growth Processes/physiology; Cyclooxygenase 1/immunology; Cyclooxygenase 2 Inhibitors/pharmacology*; Cyclooxygenase 2/biosynthesis*; Cyclooxygenase 2/genetics; Cyclooxygenase 2/metabolism; Dinoprost/immunology; Dinoprostone/immunology; Enzyme Activation; Humans; Immunoglobulin Heavy Chains/genetics; Immunoglobulin Heavy Chains/immunology; Immunohistochemistry; Indomethacin/pharmacology; Isoxazoles/pharmacology; Leukemia, B-Cell, Chronic/enzymology*; Leukemia, B-Cell, Chronic/immunology*; Leukemia, B-Cell, Chronic/pathology; Nitrobenzenes/pharmacology; Pyrazoles/pharmacology; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Sulfonamides/pharmacology; Sulfones/pharmacology; Thromboxane A2/immunology

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