CD164 and FCRL3 are highly expressed on CD4+CD26- T cells in Sezary syndrome; inverse correlation between CD164 and CD26 expression

Sezary syndrome (SS) represents a leukemic variant of cutaneous T cell lymphoma (CTCL) with circulating malignant CD4 T cells trafficking to the skin. The cell surface molecules present on malignant cells are also expressed on normal CD4 T cells. Therefore, we attempted to find a specific marker for malignant cells that would distinguish them from normal cells. Comprehensive microarray analysis of gene expression in the malignant cells indicated significantly increased levels of mRNA for cell surface markers CD164, a sialomucin found on human CD34+ hematopoietic stem cells, as well as FCRL3, a molecule present on a subset of human natural T regulatory cells. Both markers were increased in CD4 T cells from the SS patients compared to those from Mycosis Fungoides patients and healthy volunteers. Subsequent studies utilizing QPCR and flow cytometry confirmed the increased expression of CD164 and FCRL3 mainly in CD4+CD26- T cells of SS patients. Our results suggest that CD164 can serve as a marker for diagnosis as well as disease monitoring of CTCL/SS, whereas the FCRL3 expression correlates with disease progression. Gene expression was analyzed in CD4 T cells from 6 SS patients and 3 healthy donors. Samples from patients included 3 clonal patients with a defined TCR Vbeta (85-99% of CD4 T cells) of Vbeta-7,Vbeta-13.2 and Vbeta-22. The remaining 3 samples were from non-clonal patients with medium to low circulating tumor cell burdens, as defined by 20%-50% of the patients lymphocytes identifiable as CD4+ CD26- cells and/or by one micron section analysis of fixed peripheral blood buffy coats. RNA was processed as previously described and hybridized on Illumina Human WG 8v2 microarray chips. All arrays were processed in the Wistar Institute Genomics Facility.