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Gamma-Interferon Gene Expression in the Bone Marrow of Patients with Aplastic Anemia

Antonia Nistico, MD; and Neal S. Young, MD
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From the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. Requests for Reprints: Antonia Nistico, MD, 10/7C103, National Institutes of Health, Bethesda MD 20892. Acknowledgments: The authors thank Donna Vining, RN, and Janice Kimball, RN, for help in assembling the clinical data, Stacie Anderson for doing immunophenotyping and immunoassays, and Dr. Stacie Goodman for providing some marrow samples.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1994;120(6):463-469. doi:10.7326/0003-4819-120-6-199403150-00003
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Objective: To determine γ-interferon gene expression in the bone marrow of patients with aplastic anemia and controls. Most patients with acquired aplastic anemia respond to immunosuppressive therapy, implicating an immune pathophysiologic origin for this disease.

Setting: Clinical Center, National Institutes of Health.

Patients: 25 patients with aplastic anemia on presentation, 18 patients after treatment, 39 patients with other hematologic syndromes, and 20 normal controls.

Measurements and Main Results: γ-Interferon signal was detected in the bone marrow of 14 of 18 patients with severe aplasia on presentation, 4 of 7 patients with moderate aplastic anemia, and 1 of 2 patients with the paroxysmal nocturnal hemoglobinuria-aplasia syndrome. The γ-interferon gene was not expressed in marrow from 20 normal persons or in patients who had received many transfusions for chronic anemia; with pancytopenia after chemotherapy; or with marrow failure of other types, including myelodysplasia, inherited anemias, or constitutional aplastic anemia. In serial studies, γ-interferon RNA disappeared from the marrow of patients as they responded to immunosuppression; the signal was present in 3 of 4 patients who had a relapse but not in previously treated, now recovered patients. Determination of marrow γ-interferon gene expression was more specific and sensitive than concurrent determinations in peripheral blood. Quantitative titration of mRNA showed that γ-interferon expression was not a simple function of the number of lymphocytes in samples.

Conclusions: γ-Interferon expression is prevalent in acquired aplastic anemia and may be a specific marker of this disease. Local production of this inhibitory lymphokine in the target organ, the bone marrow, may be important in mediating aplastic anemia. Measurement of this lymphokine's message may be useful in distinguishing acquired aplastic anemia from other forms of bone marrow failure.


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Figure 1.
Southern analysis for γ-interferon gene expression in marrow samples from patients with various hematologic diseases.Table 1

Controls included RNA from stimulated normal peripheral blood cells. After RNA extraction, we simultaneously amplified sequences from a housekeeping gene, glyceraldehyde phosphate dehydrogenase (GAPDH), constitutively expressed in all human cells and the γ-interferon gene. γ-Interferon gene expression was detected only in the bone marrow of patients with aplastic anemia (see for summary).

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Figure 2.
Neutrophil and platelet counts in marrow donors.open circles

Only total leukocyte counts were available in the patients who had had chemotherapy ( ). AA = aplastic anemia; γ IFN = γ-interferon; FA = Fanconi anemia; MDS = myelodysplasia.

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