Lymphotoxin-alpha is an autocrine growth factor for chronic lymphocytic leukemia B cells

Leukemia
P KulmburgW Digel

Abstract

Lymphotoxin-alpha (LT), also called TNF-beta, which belongs to the 'TNF family' was originally isolated from a lymphoblastoid cell line. LT enhances the proliferation of activated B cells and augments B cell proliferation induced by IL-2. It functions as an autocrine growth factor for EBV-infected B cell lines and has been implicated in the pathogenesis of B cell malignancies. We tested the expression of LT mRNA in B-CLL and found that LT was expressed in highly purified leukemic cells in 11 out of 11 patients examined. Regulation of expression of LT mRNA is aberrant in B-CLL cells, since LT mRNA expression was not detected in fresh peripheral blood mononuclear cells or B cells identified in seven out of seven normal individuals. In addition, LT mRNA expression was detected for up to 6 days in purified unstimulated in vitro cultures of B-CLL cells. Glucocorticosteroids, that have been effectively used in the treatment of lymphoid malignancies, were added to the cultures and abrogated the LT mRNA expression after an incubation time of 12 h. Addition of recombinant LT to cultures increased proliferation of B-CLL cells while proliferation of these cells was inhibited by antisense oligonucleotides against LT mRNA. B-CLL cells cultu...Continue Reading

Citations

Apr 16, 2003·European Journal of Haematology·Yonit BomsteinMichael Lishner
Dec 26, 2001·Leukemia·R GamberaleM Giordano
Sep 28, 2007·Suicide & Life-threatening Behavior·Bonnie Klimes-DouganSusan J Harris
Jul 3, 2007·Journal of Abnormal Child Psychology·Amy M Bohnert, Judy Garber
Jan 26, 2002·The Journal of Biological Chemistry·Sandra A SchreyerRenée C LeBoeuf
Oct 19, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Long ShenJulian L Ambrus
Dec 12, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Eleonora FonteMarta Muzio

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