Sezary Syndrome Is a Malignancy of Central Memory T Cells with Skin Homing Properties, While Mycosis Fungoides Is a Malignancy of Skin Homing Effector Memory T Cells.

Abstract 3954

Poster Board III-890

The relationship between leukemic CTCL (L-CTCL), which includes Sezary Syndrome (SS), and mycosis fungoides (MF), a CTCL variant characterized by infiltration of skin, is incompletely understood. In the present study, we examined skin and/or peripheral blood from more than 300 patients with diagnoses of CTCL accrued over a five year period. We identified a subset of patients with leukemic CTCL, all of whom had absolute CD4 counts >2000, CD4/CD8 ratios of > 10, and other features of SS (loss of CD7 and/or CD26). Using specific TCR-Vb antibodies, we could identify malignant clonal populations from CD4+/CD8- peripheral blood mononuclear cells of 12 L-CTCL patients, and performed comprehensive analysis of the malignant clones by flow cytometry. With regard to skin-associated trafficking markers, we found consistently high CCR4 expression, but very heterogeneous expression of CCR6, CCR10 and CLA. Lymph-node homing molecules CCR7 and L-selectin were consistently expressed at high levels on the malignant clonal cells. CD45RA-to-CD45RO ratios, which typically distinguish between non-malignant naïve and antigen-experienced CD4 T cells, were unexpectedly variable from patient to patient. However, CD27, whose expression is lost in normal T cells upon effector/memory cell differentiation, was highly expressed by all malignant clonal cells in SS/L-CTCL. We compared this pattern to the expression of homing and maturation markers on malignant cells extracted from lesional skin of patients with MF. These cells reliably expressed CLA and CCR4, but expressed very low levels of CCR7 and L selectin. In addition, they expressed low levels of CD27. Based on this evidence, L-CTCL/SS appears to be a T central-memory cell CD4-lymphocyte malignancy that, with the exception of CCR4, has variable expression of the putative skin-homing markers CLA, CCR6, or CCR10. This is in direct contrast to MF, wherein clonal T cells in lesional skin bear uniform expression of some skin-homing markers but low expression of central memory markers. These data support a growing body of evidence that SS/L-CTCL and MF are fundamentally different malignancies, rather than different clinical stages of a single disease.