Malignant and reactive cells from human lymphomas frequently express Fas ligand but display a different sensitivity to Fas-mediated apoptosis (original) (raw)

Sensitivity: Resistance to Therapy and Apoptosis

Leukemia volume 11, pages 1868–1877 (1997) Cite this article

Abstract

Fas ligand (FasL) is capable of inducing apoptosis of lymphoid cells by cross-linking with its natural receptor, Fas. We aimed to investigate the possible role of the Fas/FasL-mediated apoptosis in the development of human lymphomas. FasL mRNA was detected by reverse transcriptase-polymerase chain reaction in 38 out of 63 lymphoma biopsy specimens representative of various subtypes of non-Hodgkin’s lymphoma (NHL) and Hodgkin’s disease. FasL was co-expressed with Fas mRNA in most cases. Flow cytometry (FACS) analysis showed a bright FasL staining in 31% to up to 75% of the total cell population from 14 out of 16 samples; the presence of the FasL protein was confirmed by Western blotting. Dual-color FACS analysis showed that FasL was expressed by T cells in B-NHLs and T-NHLs. A significant percentage of B cells in various B-NHLs also stained positively for FasL. Freshly separated neoplastic B cells from three FasL+ and one FasL− B-NHLs displayed a relative resistance to Fas-mediated apoptosis, when compared to reactive T cells isolated from the same tissue samples. In contrast, the sensitivity to Fas-mediated killing of the T cells isolated from two FasL+ T-NHLs was not uniform. These data show that (1) FasL is expressed in both neoplastic and reactive cells from a significant proportion of lymphoma cases, and (2) that the intratumoral FasL+/Fas+ reactive T cells are more sensitive to Fas-induced apoptosis than the neoplastic FasL+/Fas+ malignant B cells. A putative defect in the Fas/FasL pathway may thus favor the development of malignant B cell populations.

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Authors and Affiliations

  1. Department of Pathology, Institut Paoli-Calmettes, France
    L Xerri, E Devilard & J Hassoun
  2. INSERM U 119, France
    L Xerri, E Devilard & F Birg
  3. Immunotech SA, Marseille, France
    P Haddad

Authors

  1. L Xerri
  2. E Devilard
  3. J Hassoun
  4. P Haddad
  5. F Birg

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Xerri, L., Devilard, E., Hassoun, J. et al. Malignant and reactive cells from human lymphomas frequently express Fas ligand but display a different sensitivity to Fas-mediated apoptosis.Leukemia 11, 1868–1877 (1997). https://doi.org/10.1038/sj.leu.2400815

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