Analysis of interferon-inducible genes in cells of chronic myeloid leukemia
patients responsive or resistant to an interferon-alpha treatment
IM Clauss, B Vandenplas, MG Wathelet, C Dorval, A Delforge, J Content, P Stryckmans and GA Huez
Laboratoire de Chimie Biologique, Universite Libre de Bruxelles, Belgium.
Recombinant human interferon-alpha (IFN-alpha) can induce a hematologic
remission in patients with chronic myeloid leukemia. However, some patients
are resistant and others develop late resistance to the IFN- alpha
treatment. To understand the molecular mechanism of this resistance, we
have analyzed the expression of 10 IFN-inducible genes in the cells of
three resistant patients, two responsive patients, and six healthy
controls. Northern blot hybridizations showed that all the genes were
induced in in vitro IFN-alpha treated peripheral blood cells of the
patients and healthy controls. These genes were also inducible in
peripheral blood and bone marrow cells of two out of two resistant patients
administered an injection of IFN-alpha. We conclude that the resistance to
the IFN-alpha treatment of the chronic myeloid leukemia patients we studied
is not due to (1) the absence of induction of any of the 10 IFN-inducible
genes we studied, including the low-molecular- weight 2'-5'oligoadenylate
synthetase; (2) the presence of an antagonist of IFN-alpha in the
peripheral blood or bone marrow cells; and (3) the presence of neutralizing
anti-IFN-alpha antibodies.
Volume 76,
Issue 11,
pp. 2337-2342,
12/01/1990
Copyright © 1990 by The American Society of Hematology