Expression of serine 194-phosphorylated Fas-associated death domain protein correlates with proliferation in B-cell non-Hodgkin lymphomas

Elias Drakos, Vasiliki Leventaki, Vasileios Atsaves, Ellen J. Schlette, Pei Lin, Francisco Vega, Roberto N. Miranda, Francois Xavier Claret, L. Jeffrey Medeiros, George Z. Rassidakis

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Fas-associated death domain protein is a key component of the extrinsic apoptotic pathway. In addition, in animal models, Fas-associated death domain protein phosphorylation at serine 194 has been shown to affect cell proliferation, especially in T lymphocytes. The importance of Fas-associated death domain protein phosphorylation at serine 194 for the proliferation of B lymphocytes, however, is uncertain. Here we show in reactive lymph nodes that serine 194 phosphorylated Fas-associated death domain protein is expressed predominantly in the dark (proliferative) zone of germinal centers. In B-cell non-Hodgkin lymphoma cell lines, serine 194 phosphorylated Fas-associated death domain protein levels are substantially higher in highly proliferating cells and lower in serum-starved cells. We also used immunohistochemical analysis to assess Fas-associated death domain protein phosphorylation at serine 194 expression in 122 B-cell non-Hodgkin-type lymphomas. The mean percentage of serine 194 phosphorylated Fas-associated death domain protein positive tumor cells was 81% in Burkitt lymphoma, 41% in diffuse large B-cell lymphoma, 18% in follicular lymphoma, 18% in plasma cell myeloma, 12% in extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, 11% in mantle cell lymphoma, and 2% in chronic lymphocytic leukemia/small lymphocytic lymphoma (P <.0001, Kruskal-Wallis test). Furthermore, in chronic lymphocytic leukemia/small lymphocytic lymphoma, serine 194 phosphorylated Fas-associated death domain protein was detected predominantly in proliferation centers. In the entire study group, the percentage of cells positive for serine 194 phosphorylated Fas-associated death domain protein correlated significantly with the proliferation index Ki-67 (Spearman R = 0.9, P <.0001). These data provide evidence that serine 194 phosphorylated Fas-associated death domain protein is involved in the proliferation of normal and neoplastic B cells and has features of a novel proliferation marker.

Original languageEnglish (US)
Pages (from-to)1117-1124
Number of pages8
JournalHuman pathology
Volume42
Issue number8
DOIs
StatePublished - Aug 1 2011
Externally publishedYes

Keywords

  • B cell
  • FADD
  • Lymphomas
  • Phosphorylation, Proliferation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'Expression of serine 194-phosphorylated Fas-associated death domain protein correlates with proliferation in B-cell non-Hodgkin lymphomas'. Together they form a unique fingerprint.

  • Cite this

    Drakos, E., Leventaki, V., Atsaves, V., Schlette, E. J., Lin, P., Vega, F., Miranda, R. N., Claret, F. X., Medeiros, L. J., & Rassidakis, G. Z. (2011). Expression of serine 194-phosphorylated Fas-associated death domain protein correlates with proliferation in B-cell non-Hodgkin lymphomas. Human pathology, 42(8), 1117-1124. https://doi.org/10.1016/j.humpath.2010.11.002