Possible mechanism of action of interferon alpha in chronic B-cell malignancies

Br J Haematol. 1991 Oct:79 Suppl 1:14-6. doi: 10.1111/j.1365-2141.1991.tb08111.x.

Abstract

Recent evidence suggests that tumour necrosis factor alpha (TNF) is an autocrine growth factor for the chronic B-cell malignancies hairy cell leukaemia (HCL) and some cases of B-chronic lymphocytic leukaemia (B-CLL). Incubation with TNF in vitro has been shown to increase viability, DNA synthesis and the expression of the protooncogenes myc, fos and jun in the tumour cells from these patients. TNF in vitro also increases expression of TNF-mRNA, suggesting the existence of an autocrine growth loop for TNF in these cells. Current experiments are compatible with the hypothesis that interferon alpha (IFN) interferes with this autocrine growth loop in HCL and B-CLL by stimulating degradation of messenger RNAs (mRNAs) for a number of cytokines including that of TNF. This RNA degradation may be mediated through induction of the enzyme 2,5 oligo-A synthetase with consequent increased synthesis of 2,5 oligo-A which is known to stimulate the activity of a latent ribonuclease capable of degrading cytokine mRNAs. Circulating tumour-derived TNF may also contribute to the pancytopenia in HCL and B-CLL. Whether cytokine autocrine growth loops are important in other B-cell malignancies, e.g. myeloma and non-Hodgkin's lymphoma, and subject to IFN-stimulated breakdown needs further study.

Publication types

  • Review

MeSH terms

  • B-Lymphocytes
  • Humans
  • Interferon-alpha / therapeutic use*
  • Leukemia, Hairy Cell / therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / therapy*
  • Pancytopenia / etiology
  • Tumor Necrosis Factor-alpha / physiology

Substances

  • Interferon-alpha
  • Tumor Necrosis Factor-alpha