PML is expressed in chronic graft-versus-host disease lesions

Abstract

Summary:sera of patients with primary biliary cirrhosis (PBC) has been demonstrated, 5 raising the hypothesis that this antigen may therefore represent an autoantigenic trigger. In the The PML (for 'ProMyelocytic Leukemia') gene product is a nuclear zinc finger protein, identified when the same way, 70% of patients with other autoimmune diseases and antibodies against Sp100 (another nuclear dot antigen) chromosomal translocation fusing this gene to the retinoic acid receptor was found in acute promyelocytic leualso also had circulating anti-PML antibodies. 5 Chronic graft-versus-host disease (GVHD) is a frequent kemia. Recently, a frequent occurrence of autoantibodies against the PML protein was detected in primary and disabling complication of bone marrow transplantation whose pathogenesis is still not well understood. In contrast biliary cirrhosis (PBC) sera, suggesting that this protein could represent an autoantigenic trigger in PBC.with acute GVHD where donor anti-host T cells have been shown to be solely involved, 6,7 the pathogenesis of chronic Chronic GVHD features are close to those of PBC and in addition, antinuclear and antinucleolar antibodies GVHD seems to rely on a complex interaction between alloimmune and autoimmune mechanisms. 8,9 Liver chronic are frequently detected in patients' sera. In order to determine if an abnormal expression of PML, followed GVHD is very close to PBC. In view of this similarity and in order to determine if an abnormal expression of PML by the development of anti-PML antibodies, can be implicated in chronic GVHD pathogenesis, we studied 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 the expression of PML in the skin and the presence of circulating anti-PML antibodies. anti-PML antibodies. PML was highly expressed by the lesional skin keratinocytes, but circulating antibodies were never detected. PML is induced by interferon (IFN)␥. The expression of PML by GVHD epidermis is likely secondary to the IFN␥ produced by infiltrating Patients and methods lymphocytes. Since PML display growth suppressor properties, the role of this protein in tissue lesions is disPatients cussed. Keywords: GVHD; PML; skin Seven patients with chronic GVHD included in this study are summarized in Table 1. All had cutaneous lesions and four also had liver GVHD. Cutaneous biopsies were done The non-random chromosomal translocation t(15;17) on the lesions and when possible on non-lesional skin also. characteristic of the acute promyelocytic leukemia (APL) Positive controls were obtained from patients with psoriasis has led to the identification of a fusion between the PML (a disease already shown to be associated with PML gene (for 'ProMyelocytic Leukemia') present on chromoexpression in keratinocytes). Negative controls were done some 15 and the retinoic acid receptor (RAR␣) on chromoon normal skin specimens obtained from breast ...

Overexpression of Promyelocytic Leukemia Protein and Alteration of PML Nuclear Bodies in Early Stage of Hepatocarcinogenesis

“…The PML expression was considerably upregulated in inflammatory tissues such as hepatitis as well as during either normal or pathological proliferative states including benign or malignant tumors (4,(10)(11)(12)(13). In most of malignant solid tumors examined, the PML was markedly overexpressed and organization of PML NBs was not disturbed, unlike in cases of APL (13)(14)(15).…”

Expression of promyelocytic leukaemia protein in thyroid neoplasms

“…The observation indicates that the PML may not be associated with tumourigenesis of the follicular neoplasm of the thyroid. 16–19 Because only one case of overt follicular carcinoma was included in this study, PML expression in more cases of frankly invasive follicular carcinomas should be studied to define better the role of the PML in the follicular carcinogenesis.…”

Genes Highly Expressed in the Early Phase of Murine Graft-versus-Host Reaction

“…Although it is speculated that PRCC may function in a signaling cascade because it possesses a proline-rich domain, its physiological and pathophysiological roles still remain uncertain (50). The increased expression levels of PRCC in the liver of the GVHR mice, as well as high expression of Bcl-2 and PML in the target tissues of GVHR, seem to make the functional relevance of some cancerrelated genes to GVHR worth investigating (51,52).…”