title: Biological effects of bexarotene in cutaneous T-cell lymphoma.
abstract: 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.
authors.affiliation: Department of Dermatology, University of Pennsylvania, Philadelphia, PA 19104, USA. jbudgin@vet.upenn.edu
authors.forename: Jeanne B
authors.initials: JB
authors.lastname: Budgin
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Richardson
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Newton
authors.forename: Maria
authors.initials: M
authors.lastname: Wysocka
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Zaki
authors.forename: Bernice
authors.initials: B
authors.lastname: Benoit
authors.forename: Alain H
authors.initials: AH
authors.lastname: Rook
mesh_terms: 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
chemical_list: D016207:Cytokines; D016898:Interferon-alpha; D013764:Tetrahydronaphthalenes; D015847:Interleukin-4; D007371:Interferon-gamma; D000077610:Bexarotene