1. ¹Department of Pathology, UCLA School of Medicine, Los Angeles, California
2. ²Department of Medicine, UCLA School of Medicine, Los Angeles, California
3. ³Jonsson Comprehensive Cancer Center, UCLA School of Medicine, Los Angeles, California
4. ⁴Department of Dermatology, University of Zurich Medical School, Zurich, Switzerland

Correspondence: Linda G. Baum, M.D., Ph.D., Department of Pathology, UCLA School of Medicine, 10833 Le Conte Ave., Los Angeles, CA 90095-1732; fax: 310-206-0657; e-mail: lbaum@mednet.ucla.edu.

Accepted 1 March 2003.

Abstract

Sezary cells, the malignant T cells in mycosis fungoides/Sezary syndrome, resist a variety of apoptosis-inducing agents, a feature that contributes to the poor response to therapy in mycosis fungoides. Galectin-1 is a mammalian lectin that triggers T cell apoptosis. For T cells to be susceptible to galectin-1–induced apoptosis, the T cells must express specific glycoprotein receptors, such as CD7, that bear the specific oligosaccharides recognized by galectin-1. Because Sezary cells are characteristically CD7^-, lack of CD7 expression has been proposed to render Sezary cells resistant to galectin-1–induced death. However, the role played by aberrant cell surface glycosylation in resistance of Sezary cells to galectin-1 has not been examined. In this study, we demonstrated abundant galectin-1 in mycosis fungoides skin lesions, indicating that Sezary cells are exposed to galectin-1 in vivo. To determine specific characteristics of Sezary cells that contribute to galectin-1 resistance, we assessed CD7 expression and cell surface glycosylation of Sezary cells in mycosis fungoides lesions and of four Sezary T cell lines. Sezary cells in primary lesions and Sezary T cell lines demonstrated a characteristic "glycotype" with sialylated core 1 O-glycans that promote galectin-1 resistance. Expression of CD7 was necessary but not sufficient for galectin-1–induced death of Sezary cell lines. In addition, CD7^- Sezary cell lines, and Sezary cells within mycosis fungoides lesions, expressed galectin-1, whereas CD7-positive Sezary cell lines did not express galectin-1. We propose that both loss of CD7 expression and altered cellular glycosylation contribute to apoptosis resistance of malignant T cells in mycosis fungoides.