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Prepublished online as a Blood First Edition Paper on December 27, 2002; DOI 10.1182/blood-2002-11-3335.

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Blood, 1 May 2003, Vol. 101, No. 9, pp. 3514-3519

IMMUNOBIOLOGY

The PML gene is not involved in the regulation of MHC class I expression in human cell lines

Silvia Bruno, Fabio Ghiotto, Franco Fais, Marta Fagioli, Lucilla Luzi, Pier Giuseppe Pelicci, Carlo Enrico Grossi, and Ermanno Ciccone

From the Department of Experimental Medicine, Section of Human Anatomy, Genoa University, Genoa, Italy; the Department of Experimental Oncology, European Institute of Oncology, Milan, Italy; the Department of Clinical and Experimental Medicine, Section of Internal Medicine and Oncological Sciences, Perugia University, Perugia, Italy; and the Fondazione Italiana per la Ricerca sul Cancro, Institute for Molecular Oncology, Milan, Italy.

The promyelocytic leukemia gene, PML, is a growth and transformation suppressor. An additional role for PML as a regulator of major histocompatibility complex (MHC) class I antigen presentation has been proposed in a murine model, which would account for evasion from host immunity of tumors bearing malfunctioning PML, such as acute promyelocytic leukemia. Here we investigated a possible role of PML for the control MHC class I expression in human cells. PML function was perturbed in human cell lines either by PML/RARalpha transfection or by PML- specific RNA interference. Impairment of wild-type PML function was proved by a microspeckled disassembly of nuclear bodies (NBs), where the protein is normally localized, or by their complete disappearance. However, no MHC class I down-regulation was observed in both instances. We next constructed a PML mutant, PML mut ex3, that is a human homolog of the murine PML mutant, truncated in exon 3, that was shown to down-regulate murine MHC class I. PML mut ex3 transfected in human cell lines exerted a dominant-negative effect since no PML molecules were detected in NBs but, instead, in perinuclear and cytoplasmic larger dotlike structures. Nevertheless, no down-regulation of MHC class I expression was evident. Moreover, neither transfection with PML mut ex3 nor PML-specific RNA interference affected the ability of gamma -interferon to up-regulate MHC class I expression. We conclude that, in human cell lines, PML is not involved directly in the regulation of MHC class I expression.

© 2003 by The American Society of Hematology.
 

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