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TNF-alpha and IFN-gamma are overexpressed in the bone marrow of Fanconi anemia patients and TNF-alpha suppresses erythropoiesis in vitro
- Dufour, C (author)
- Corcione, A (author)
-
- Svahn, Johan (author)
- Lund University,Lunds universitet,Pediatrik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Paediatrics (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Haupt, R (author)
- Poggi, V (author)
- Beka'ssy, AN (author)
- Scime, R (author)
- Pistorio, A (author)
- Pistoia, V (author)
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- (creator_code:org_t)
- American Society of Hematology, 2003
- 2003
- English.
- In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 102:6, s. 2053-2059
- Journal article (peer-reviewed)
Abstract
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- In Fanconi anemia (FA) C mice tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) have key roles in the pathogenesis of bone marrow failure. In FA subjects TNF-alpha was found to be increased in the serum and overproduced by patient-derived B-cell lines. In acquired aplastic anemia, a disease in which, similarly to FA, marrow failure occurs, TNF-alpha and IFN-gamma act as late mediators of the stem cell damage and are overexpressed in patient marrow lymphocytes. This study evaluated in marrow mononuclear cells (MNCs) of patients with FA, the expression of negative modulators of the hematopoiesis, such as TNF-alpha, IFN-gamma, macrophage inflammatory protein 1alpha (MIP-1alpha), and surface Fas ligand, and the role of TNF-alpha on FA erythropoiesis in vitro. TNF-alpha and IFN-gamma were significantly overexpressed in stimulated marrow MNCs of FA patients as compared to healthy controls. MIP-1alpha and Fas ligand were undetectable in patients and controls. In bone marrow cultures, the addition of anti-TNF-alpha increased the size and significantly increased the number of erythroid colony-forming units and erythroid burst-forming units grown from FA patients but not from healthy controls. This indicates that FA subjects have a marrow TNF-alpha activity that inhibits erythropoiesis in vitro. TNF-alpha has a relevant role in the pathogenesis of erythroid failure in FA patients.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
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- Dufour, C
- Corcione, A
- Svahn, Johan
- Haupt, R
- Poggi, V
- Beka'ssy, AN
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- Scime, R
- Pistorio, A
- Pistoia, V
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
- MEDICAL AND HEAL ...
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- and Hematology
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- Blood
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- Lund University
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