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Interferon-gamma gene expression in unstimulated bone marrow mononuclear
cells predicts a good response to cyclosporine therapy in aplastic anemia
S Nakao, M Yamaguchi, S Shiobara, T Yokoi, T Miyawaki, T Taniguchi and T Matsuda
Third Department of Medicine, Kanazawa University School of Medicine,
Japan.
Cyclosporine (CyA) therapy has been shown to be effective in some patients
with aplastic anemia. In an attempt to characterize aplastic patients
likely to benefit from CyA therapy, we examined bone marrow mononuclear
cells (BMMC) obtained before therapy from 23 patients with aplastic anemia,
who were treated with CyA alone. Expression of four myelosuppressive
cytokines, including tumor necrosis factor (TNF), lymphotoxin, macrophage
inflammatory protein-1 alpha (MIP-1 alpha), and interferon-gamma
(IFN-gamma) was examined using polymerase chain reaction (PCR)-assisted
messenger RNA (mRNA) amplification. mRNA for TNF, lymphotoxin, and MIP-1
alpha was readily detectable at variable levels in BMMC from normal and
transfused controls as well as in BMMC from aplastic patients. In contrast,
IFN-gamma mRNA was only demonstrable in BMMC from some patients with
aplastic anemia, irrespective of a history of transfusions. Of 13 patients
who responded to CyA therapy and achieved transfusion-independence,
IFN-gamma mRNA was detected in 12 patients, whereas the mRNA was only
detectable in 3 of 10 patients refractory to CyA therapy (P = .003,
Fisher's exact test). Follow-up examination of BMMC obtained from seven
CyA-responding patients after hematologic remission showed disappearance of
IFN-gamma mRNA in four patients. These results suggest that detection of
IFN- gamma gene expression in pretreatment BMMC from aplastic patients
using PCR may be helpful in predicting a good response to CyA therapy.
Volume 79,
Issue 10,
pp. 2532-2535,
05/15/1992
Copyright © 1992 by The American Society of Hematology
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