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PML is expressed in chronic graft-versus-host disease lesions
S Aractingi1, H de Thé, E Gluckman
1DRM-DSV, CEA, Hôpital Saint-Louis, Paris, France.
Abstract:
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.
Insights
ProMyelocytic Leukemia (PML) protein is highly expressed in chronic GVHD skin lesions, likely due to interferon-gamma. However, circulating anti-PML antibodies were not detected in these patients.
Area of Science:
- Immunology
- Oncology
- Dermatology
Background:
- The ProMyelocytic Leukemia (PML) gene product is a nuclear zinc finger protein.
- Autoantibodies against PML are frequent in primary biliary cirrhosis (PBC) sera.
- Chronic graft-versus-host disease (GVHD) shares features with PBC, including antinuclear antibodies.
Purpose of the Study:
- To investigate the role of abnormal PML expression and anti-PML antibodies in chronic GVHD pathogenesis.
- To determine if PML protein expression is altered in the skin of chronic GVHD patients.
- To assess the presence of circulating anti-PML antibodies in chronic GVHD patients.
Main Methods:
- Studied PML expression in skin biopsies from seven chronic GVHD patients.
- Assessed the presence of circulating anti-PML antibodies in the same patients.
- Analyzed PML expression in lesional skin keratinocytes.
Main Results:
- PML protein was highly expressed in the keratinocytes of lesional skin from chronic GVHD patients.
- Circulating anti-PML antibodies were not detected in any of the studied patients.
- PML expression is induced by interferon-gamma (IFN-γ), suggesting it's secondary to lymphocyte-produced IFN-γ in GVHD skin.
Conclusions:
- Abnormal PML expression occurs in chronic GVHD skin lesions.
- The absence of anti-PML antibodies suggests they are not involved in the pathogenesis of chronic GVHD.
- PML's role in tissue lesions, given its growth suppressor properties, warrants further discussion.