Polymorphism of the tumour necrosis factor-alpha and lymphotoxin-alpha genes in chronic lymphocytic leukaemia

Judith Demeter, Franz Porzsolt, Stephanie Rämisch, Dorothee Schmidt, Mathias Schmid, Gerald Messer

Research output: Article

65 Citations (Scopus)

Abstract

The neoplastic cells of CLL are able to produce TNF which is known to stimulate the proliferation of CLL cells in an autocrine and paracrine manner. Genetic polymorphism of molecules of the TNF ligand superfamily has been described and certain alleles were suspected to predispose to variant biological responses. Previously, the rare allele TNFB*1 of the TNF-β/lymphotoxin (LT)-α gene (NcoI, asparagine at amino acid position 26) was found to be associated with a stronger LT-α response of PBMC in vitro. We now report on a significant increase of the allele TNF1 (TNFA - 308 G) of the TNF-α promoter/enhancer polymorphism in a group of 73 CLL patients when compared to healthy individuals (RR = 3.18, 95% confidence interval 1.57-8.3; P = 0.006). The allelic distribution of the TNF-β/LT-α NcoI polymorphism did not differ significantly from randomized healthy controls. On the other hand, the frequency of the allele TNFB*2 was increased in CLL patients with advanced clinical stage (P = 0.004). These findings indicate immunogenetic associations involving polymorphisms of cytokine genes serving as paracrine and autocrine growth factors, which thus can contribute to the pathogenesis of the TNF/LT-sensitive haematological malignancy CLL.

Original languageEnglish
Pages (from-to)107-112
Number of pages6
JournalBritish Journal of Haematology
Volume97
Issue number1
DOIs
Publication statusPublished - jan. 1 1997

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ASJC Scopus subject areas

  • Hematology

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