CD164 and FCRL3 are highly expressed on CD4+CD26- T cells in Sézary syndrome patients.

Maria Wysocka, Andrew V Kossenkov, Bernice M Benoit, Andrea B Troxel, Elisha Singer, Andras Schaffer, Brian Kim, Tzvete Dentchev, Satoshi Nagata, Tomoko Ise, Louise C Showe, Alain H Rook
Author Information
  1. Maria Wysocka: Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA. Electronic address: mwysocka@mail.med.upenn.edu.
  2. Andrew V Kossenkov: The Wistar Institute, Philadelphia, Pennsylvania, USA.
  3. Bernice M Benoit: Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  4. Andrea B Troxel: Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  5. Elisha Singer: Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  6. Andras Schaffer: Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  7. Brian Kim: Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  8. Tzvete Dentchev: Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  9. Satoshi Nagata: Cancer Biology Research Center, Sanford Research/USD, Sioux Falls, South Dakota, USA.
  10. Tomoko Ise: Cancer Biology Research Center, Sanford Research/USD, Sioux Falls, South Dakota, USA.
  11. Louise C Showe: The Wistar Institute, Philadelphia, Pennsylvania, USA.
  12. Alain H Rook: Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Abstract

Sézary syndrome (SS) cells express cell surface molecules also found on normal activated CD4 T cells. In an effort to find a more specific surface marker for malignant SS cells, a microarray analysis of gene expression was performed. Results showed significantly increased levels of mRNA for CD164, a sialomucin found on human CD34+ hematopoietic stem cells, and FCRL3, a molecule present on a subset of human natural T regulatory cells. Both markers were increased in CD4 T cells from SS patients compared with healthy donors (HD). Flow cytometry studies confirmed the increased expression of CD164 and FCRL3 primarily on CD4+CD26- T cells of SS patients. Importantly, a statistically significant correlation was found between an elevated percentage of CD4+CD164+ T cells and an elevated percentage of CD4+CD26- T cells in all tested SS patients but not in patients with mycosis fungoides and atopic dermatitis or HD. FCRL3 expression was significantly increased only in patients with high tumor burden. CD4+CD164+ cells displayed cerebriform morphology and their loss correlated with clinical improvement in treated patients. Our results suggest that CD164 can serve as a marker for diagnosis and for monitoring progression of cutaneous T-cell lymphoma (CTCL)/SS and that FCRL3 expression correlates with a high circulating tumor burden.

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Grants

  1. K08 AR065577/NIAMS NIH HHS
  2. R01CA122569/NCI NIH HHS
  3. R01 CA 132098/NCI NIH HHS
  4. R01 CA132098/NCI NIH HHS
  5. P30 CA010815/NCI NIH HHS
  6. R01 CA122569/NCI NIH HHS
  7. P30 CA016520/NCI NIH HHS
  8. 1P20RR024219-01A2/NCRR NIH HHS
  9. P30 CA013696/NCI NIH HHS
  10. P20 RR024219/NCRR NIH HHS

MeSH Term

Biomarkers
CD4-Positive T-Lymphocytes
Cell Shape
Dipeptidyl Peptidase 4
Disease Progression
Endolyn
Flow Cytometry
Humans
Membrane Glycoproteins
Microfilament Proteins
Neoplastic Cells, Circulating
Receptors, Immunologic
Sezary Syndrome
Transcriptome

Chemicals

Biomarkers
Endolyn
FCRL3 protein, human
Membrane Glycoproteins
Microfilament Proteins
Receptors, Immunologic
plastin
DPP4 protein, human
Dipeptidyl Peptidase 4

Word Cloud

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