Interferon-α resistance in a cutaneous T-cell lymphoma cell line is associated with lack of STAT1 expression

Wenn H. Sun*, Carlos Pabon, Yazan Alsayed, Paul P. Huang, Sara Jandeska, Shahab Uddin, Leonidas C. Platanias, Steven T. Rosen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

145 Scopus citations

Abstract

Interferon-alpha (IFNα) mediates its biological effects through activation of the JAK-STAT signaling pathway and it has been shown to be one of most effective therapeutic agents for a number of hematological malignancies, including cutaneous T-cell lymphoma (CTCL). Nevertheless, its efficacy is limited by the development of clinical resistance but the reasons for resistance in CTCL are unknown. Here, we report the development of an IFNα-resistant CTCL cell line (HUT78R), characterized by its ability to proliferate in high concentration of recombinant IFNα, which can be used as a model system to study IFN resistance. The levels of IFN receptor expression and binding affinity were found to be comparable between the parental sensitive (HUT78S) and resistant (HUT78R) cells. However, IFNα stimulation failed to induce interferon-stimulated gene factor 3 (ISGF3) complex formation in HUT78R cells. In addition, the expression of the IFN-inducible 2-5 OAS gene was significantly reduced in HUT78R cells, suggesting the presence of a defect in the Jak-STAT signaling pathway. Our results showed that the IFNα-activated form of a latent transcriptional factor STAT1 was not found in HUT78R cells, whereas activated STAT2 and STAT3 were clearly detectable. By Western blotting and reverse transcriptase-polymerase chain reaction (RT-PCR) analyses, we found that HUT78R calls do not express any STAT1 protein or mRNA, suggesting the possibility of a null mutation in the STAT1 gene. Resistance to the growth inhibitory effect of IFNα in CTCL cells may result from lack of STAT1 expression.

Original languageEnglish (US)
Pages (from-to)570-576
Number of pages7
JournalBlood
Volume91
Issue number2
DOIs
StatePublished - Jan 15 1998

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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