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

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


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.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Apoptosis / physiology
  • Biomarkers / metabolism
  • Calcineurin / metabolism
  • Calcium / metabolism
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Survival / physiology
  • Female
  • Gene Expression Regulation, Neoplastic / physiology
  • Humans
  • Jurkat Cells
  • Lymphoma, T-Cell / genetics
  • Lymphoma, T-Cell / pathology
  • Lymphoma, T-Cell / physiopathology*
  • Male
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / metabolism*
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / metabolism*
  • Middle Aged
  • NFATC Transcription Factors / metabolism
  • Sezary Syndrome / genetics
  • Sezary Syndrome / pathology
  • Sezary Syndrome / physiopathology*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / pathology
  • Skin Neoplasms / physiopathology*
  • Transcriptional Activation / physiology


  • Biomarkers
  • Membrane Glycoproteins
  • Microfilament Proteins
  • NFATC Transcription Factors
  • plastin
  • Calcineurin
  • Calcium