PML is expressed in chronic graft-versus-host disease lesions.
The PML (for 'ProMyelocytic Leukemia') gene product is a nuclear zinc finger protein, identified when the chromosomal translocation fusing this gene to the retinoic acid receptor was found in acute promyelocytic leukemia. Recently, a frequent occurrence of autoantibodies against the PML protein was detected in primary biliary cirrhosis (PBC) sera, suggesting that this protein could represent an autoantigenic trigger in PBC. Chronic GVHD features are close to those of PBC and in addition, antinuclear and antinucleolar antibodies are frequently detected in patients' sera. In order to determine if an abnormal expression of PML, followed by the development of anti-PML antibodies, can be implicated in chronic GVHD pathogenesis, we studied the expression of PML in the skin of seven patients with chronic GVHD as well as the presence of circulating anti-PML antibodies. PML was highly expressed by the lesional skin keratinocytes, but circulating antibodies were never detected. PML is induced by interferon (IFN) gamma. The expression of PML by GVHD epidermis is likely secondary to the IFN gamma produced by infiltrating lymphocytes. Since PML display growth suppressor properties, the role of this protein in tissue lesions is discussed.
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DRM-DSV, CEA, Hôpital Saint-Louis, Paris, France.
de Thé
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Gluckman
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Le Goué
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Carosela
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D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000097:blood; D002908:Chronic Disease; D005260:Female; D006086:Graft vs Host Disease / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D015603:Keratinocytes / Q000737:chemistry*; D008297:Male; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors / Q000032:analysis* / Q000276:immunology; D025521:Tumor Suppressor Proteins
D000906:Antibodies; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D007371:Interferon-gamma