Biological effects of bexarotene in cutaneous T-cell lymphoma.
OBJECTIVE
To determine the effects of bexarotene on malignant T cells isolated from the peripheral blood of patients with the leukemic variant of cutaneous T-cell lymphoma (Sézary syndrome).


METHODS
Peripheral blood mononuclear cells from 9 patients with Sézary syndrome and a high burden of circulating malignant T cells (>50% of peripheral blood mononuclear cells) and 6 healthy volunteers underwent evaluation at a university medical center, to test the effects of bexarotene on T cells.


METHODS
The capacity of bexarotene to induce apoptosis and its effects on T-cell cytokine production from peripheral blood lymphocytes isolated from patients with Sézary syndrome.


RESULTS
Bexarotene produced dose-dependent apoptosis of peripheral blood T cells from patients with Sézary syndrome. The T cells from approximately two thirds of patients were consistently sensitive to bexarotene, whereas those from the remaining one third of patients were consistently resistant to the apoptotic effects of bexarotene. Bexarotene inhibited mitogen-induced interleukin 4 production by the peripheral blood cells of patients with Sézary syndrome, and this effect correlated with sensitivity of patients' cells to apoptosis. In contrast to the retinoic acid receptor-specific retinoid, all-trans retinoic acid, bexarotene does not induce the augmentation of interferon gamma production.


CONCLUSIONS
Bexarotene induces apoptosis of malignant T cells from patients with Sézary syndrome, but the cells from a proportion of patients are resistant to the apoptotic effects. Interleukin 4 production, which can play a role in the systemic immunosuppression that characterizes advancing Sézary syndrome, may be inhibited by bexarotene.
Budgin
Jeanne B
JB
Department of Dermatology, University of Pennsylvania, Philadelphia, PA 19104, USA. jbudgin@vet.upenn.edu
Richardson
Stephen K
SK
Newton
Sarah B
SB
Wysocka
Maria
M
Zaki
Mohamed H
MH
Benoit
Bernice
B
Rook
Alain H
AH
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D000077610:Bexarotene; D016022:Case-Control Studies; D016207:Cytokines / Q000032:analysis / Q000378:metabolism*; D004357:Drug Synergism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D008297:Male; D012016:Reference Values; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012751:Sezary Syndrome / Q000097:blood / Q000473:pathology*; D012878:Skin Neoplasms / Q000097:blood / Q000473:pathology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D016207:Cytokines; D016898:Interferon-alpha; D013764:Tetrahydronaphthalenes; D015847:Interleukin-4; D007371:Interferon-gamma; D000077610:Bexarotene