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Elevated levels of biologically active soluble CD40 ligand in the serum of patients with chronic lymphocytic leukaemia
Author(s) -
Younes Anas,
Snell Virginia,
Consoli Ugo,
Clodi Katharina,
Zhao Shourong,
Palmer J. Lynn,
Thomas Elaine K.,
Armitage Richard J.,
Andreeff Michael
Publication year - 1998
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1998.00522.x
Subject(s) - fludarabine , cd40 , fas ligand , apoptosis , chronic lymphocytic leukemia , jurkat cells , cancer research , immunology , medicine , programmed cell death , in vitro , biology , chemotherapy , t cell , immune system , leukemia , cytotoxic t cell , biochemistry , cyclophosphamide
Chronic lymphocytic leukaemia (CLL) is an indolent lymphoproliferative disorder manifested by low growth fraction and prolonged survival of the malignant cells. The mechanisms that enable CLL cells to live longer and to resist apoptosis remain unclear. Because the malignant CLL cells express CD40 and Fas receptors, which can transduce cell‐survival and cell‐death signals, we examined the role of CD40 in the growth regulation of CLL cells and its interaction with Fas‐mediated and fludarabine‐induced apoptosis in vitro . Primary CLL cells underwent spontaneous apoptosis in culture, which was enhanced by exogenous human Fas ligand (FasL) or fludarabine. Exogenous CD40L rescued CLL cells from spontaneous apoptosis in a dose‐dependent manner, and caused CLL cells to resist apoptosis induced by FasL or fludarabine. Patients' autologous plasma rescued CLL cells from spontaneous apoptosis, an effect that could be reversed with anti‐CD40 ligand (CD40L) antibodies. The levels of soluble CD40 ligand in the sera of 51 CLL patients and 55 healthy donors were determined by enzyme‐linked immunosorbent assay. The mean soluble CD40L level in normal donors was 0.29 ng/ml compared to a mean value of 0.80 ng/ml in CLL patients ( P < 0.001). CD40L up‐regulated bcl‐X L mRNA but not bcl‐2 in CLL cells within 3–6 h in culture. Our results demonstrated that serum of patients with CLL contained elevated levels of biologically active soluble CD40L, and that CD40L can prolong survival of CLL cells and mediate their resistance to FasL and fludarabine in vitro .