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Interferon- 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, and
Steven T. Rosen
From the Division of Dermatology, Department of Pediatrics,
Northwestern University Medical School, Chicago, IL; Robert Lurie
Cancer Center, Northwestern University Medical School, Chicago, IL; and
the Section of Hematology/Oncology, University of Illinois at Chicago,
Chicago, IL.
Interferon-alpha (IFN ) 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 IFN-resistant CTCL cell line (HUT78R),
characterized by its ability to proliferate in high concentration of
recombinant IFN, 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, IFN 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
IFN-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 cells 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 IFN in CTCL cells may result from lack of STAT1 expression.
Blood, Vol. 91 No. 2 (January 15), 1998:
pp. 570-576
© 1998 by The American Society of Hematology.
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