Regulation of T-Plastin Expression by Promoter Hypomethylation in Primary Cutaneous T-Cell Lymphoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-08

AUTHORS

Christine L Jones, Silvia Ferreira, Robert C T McKenzie, Isabella Tosi, Jacqueline A Caesar, Martine Bagot, Sean J Whittaker, Tracey J Mitchell

ABSTRACT

T-plastin (PLS3) is an actin-bundling protein normally expressed in epithelial cells but absent in cells of hematopoietic origin. Aberrant PLS3 expression has been demonstrated in lymphocytes from Sézary syndrome (SS) patients and has been proposed as a biomarker for SS; however, the mechanism underlying dysregulation of PLS3 has not been determined. In this study, PLS3 mRNA expression was demonstrated in 21/35 (60%) SS patients and in 3/8 (38%) mycosis fungoides patients, all of whom had clonal blood involvement. No evidence for PLS3 mutations within coding or promoter regions was found, but significant hypomethylation of CpG dinucleotides 95-99 within the PLS3 CpG island was observed and this was restricted to the PLS3+ population. A polyclonal antibody specific to PLS3 was raised to examine coexpression of PLS3 with a panel of T-cell differentiation markers. All PLS3+ cells were CD3+CD4+ and CD26-, suggesting that loss of CD26 is consistently associated with gain of PLS3, whereas all other markers were distributed heterogeneously. However, a patient-specific TCR copy number assay also demonstrated heterogeneity in PLS3 expression in tumor cell populations. Importantly, our findings demonstrate PLS3 expression in the majority of SS patients and provide insight into the molecular regulation of PLS3 expression in CTCL. More... »

PAGES

2042-2049

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/jid.2012.106

DOI

http://dx.doi.org/10.1038/jid.2012.106

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1030129333

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22495182


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