The NFATc1 transcription factor is widely expressed in white cells and translocates from the cytoplasm to the nucleus in a subset of human lymphomas.
Stimulation of lymphoid cells via their surface receptors triggers signalling pathways that terminate in the nucleus, where they induce alterations in gene transcription. Nuclear factor of activated T cells (NFAT) transcription factors, involved in a major Ca2+-dependent signalling pathway, normally reside in the cytoplasm but re-locate to the nucleus when activation of the pathway (e.g. following ligation of antigen receptors) leads to their dephosphorylation. This study found that one member of the NFAT family (NFATc1/NFAT2) can be detected in routine biopsy samples, where it is seen in essentially all lymphoid cells, but is absent from the great majority of non-haematopoietic cells. An immunohistological evaluation of NFATc1 in almost 300 lymphomas showed that most neoplastic lymphoid cells also express NFATc1 as a cytoplasmic constituent, although it is absent in classical Hodgkin's disease and plasma cell proliferations. Of particular interest was the finding that NFATc1 was relocated to the nucleus in a minority of lymphoid neoplasms (usually diffuse large B-cell lymphomas or Burkitt lymphoma), presumably reflecting activation of the NFAT pathway. It would be of interest to correlate this feature with patterns of gene expression and also with prognosis, since it may identify a subset of human lymphoma that is distinct in its molecular and clinical features.
Marafioti
Teresa
T
Leukaemia Research Fund Immunodiagnostics Unit, Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Oxford, UK. teresa.marafioti@ndcls.ox.ac.uk
Marafiot
Teresa
T
Pozzobon
Michela
M
Hansmann
Martin-Leo
ML
Ventura
Roland
R
Pileri
Stefano A
SA
Roberton
Helen
H
Gesk
Stefan
S
Gaulard
Philippe
P
Barth
Thomas F E
TF
Du
Ming Q
MQ
Leoncini
Lorenzo
L
Möller
Peter
P
Natkunam
Yasodha
Y
Siebert
Reiner
R
Mason
David Y
DY
D014408:Biomarkers, Tumor / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002869:Chromosome Aberrations; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006689:Hodgkin Disease / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D007962:Leukocytes / Q000378:metabolism*; D008221:Lymphoid Tissue / Q000378:metabolism; D008223:Lymphoma / Q000378:metabolism*; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism; D050778:NFATC Transcription Factors; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; C494003:NFATC1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors