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PML Nuclear Bodies and SATB1 Are Associated with HLA Class I Expression in EBV+ Hodgkin Lymphoma
Authors:Yuxuan Liu  Anke van den Berg  Rianne Veenstra  Bea Rutgers  Ilja Nolte  Gustaaf van Imhoff  Lydia Visser  Arjan Diepstra
Institution:1. Department of Pathology & Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.; 2. Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.; 3. Department of Hematology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.; University of Birmingham, United Kingdom,
Abstract:Tumor cells of classical Hodgkin lymphoma (cHL) are characterized by a general loss of B cell phenotype, whereas antigen presenting properties are commonly retained. HLA class I is expressed in most EBV+ cHL cases, with an even enhanced expression in a proportion of the cases. Promyelocytic leukemia protein (PML) and special AT-rich region binding protein 1 (SATB1) are two global chromatin organizing proteins that have been shown to regulate HLA class I expression in Jurkat cells. We analyzed HLA class I, number of PML nuclear bodies (NBs) and SATB1 expression in tumor cells of 54 EBV+ cHL cases and used 27 EBV− cHL cases as controls. There was a significant difference in presence of HLA class I staining between EBV+ and EBV− cases (p<0.0001). We observed normal HLA class I expression in 35% of the EBV+ and in 19% of the EBV− cases. A stronger than normal HLA class I expression was observed in approximately 40% of EBV+ cHL and not in EBV− cHL cases. 36 EBV+ cHL cases contained less than 10 PML-NBs per tumor cell, whereas 16 cases contained more than 10 PML-NBs. The number of PML-NBs was positively correlated to the level of HLA class I expression (p<0.01). The percentage of SATB1 positive cells varied between 0% to 100% in tumor cells and was inversely correlated with the level of HLA class I expression, but only between normal and strong expression (p<0.05). Multivariable analysis indicated that the number of PML-NBs and the percentage of SATB1+ tumor cells are independent factors affecting HLA class I expression in EBV+ cHL. In conclusion, both PML and SATB1 are correlated to HLA class I expression levels in EBV+ cHL.
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