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Blood. 2012 Jul 5;120(1):143-54. doi: 10.1182/blood-2011-09-379156. Epub 2012 May 24.

Inducible expression and pathophysiologic functions of T-plastin in cutaneous T-cell lymphoma.

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1
Centre de Recherche sur la Peau, Université Paris Diderot, Hôpital Saint-Louis, Paris, France.

Abstract

A molecular feature of Sézary syndrome (SS) is the abnormal expression of T-plastin by malignant T cells. Herein, we investigated the molecular mechanisms involved in T-plastin synthesis and the functions of this actin-binding protein, with a special interest in chemoresistance and migration. We confirm the specific expression of T-plastin in peripheral blood lymphocytes (PBLs) from SS patients and its total absence in PBLs from patients with mycosis fungoides, inflammatory cutaneous or hematologic diseases, and from healthy volunteers. Only 3 of 4 SS patients did constitutively express T-plastin. To assess whether T-plastin expression was inducible, T-plastin-negative PBLs were stimulated by phorbol 12-myristate 13-acetate and ionomycin. Our results demonstrate that T-plastin synthesis was induced in negative PBLs from SS patients, other studied patients, and healthy volunteers. Both constitutive and calcium-induced T-plastin expression was down-regulated by calcineurin inhibitors and involved nuclear factor of activated T cells transcription pathway. Constitutive T-plastin expression in SS was associated with resistance to etoposide-induced apoptosis and cell migration toward chemokines (TARC/CCL17, IP-10). In conclusion, T-plastin is a marker restricted to malignant lymphocytes from SS patients and plays a role for cell survival and migration. This opens new strategies for the treatment of SS advanced stages.

PMID:
22627769
DOI:
10.1182/blood-2011-09-379156
[Indexed for MEDLINE]
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