title: Reversible resistance to apoptosis in cutaneous T cell lymphoma.
abstract: Mycosis fungoides and its leukemic variant, Sézary syndrome, represent the most common forms of cutaneous T cell lymphomas (CTCL). These disorders are clonal neoplasms characterized by the progressive accumulation of cells that resemble activated/memory CD4+ T cells. Unlike their normal counterparts, these malignant lymphocytes have prolonged life spans and are resistant to dying following treatment with most chemotherapeutic agents. This suggests that CTCL undergo abnormal programmed cell death; however, data regarding apoptotic defects in CTCL are limited. Regulation of apoptosis in lymphocytes that regularly undergo clonal expansion is necessarily complex and will be reviewed here. Clonally expanded lymphocytes rely primarily on Fas-mediated pathways to initiate apoptosis. Factors leading to the resistance of apoptosis in CTCL and new therapeutic approaches for reversing this resistance will be discussed, including the important role that the Fas death pathway may play in the pathogenesis and treatment of CTCL.
authors.affiliation: Department of Pediatric Oncology, University of Colorado Health Sciences Center, Denver 80218, USA. meech.sandra@tchden.org
authors.forename: S J
authors.initials: SJ
authors.lastname: Meech
authors.forename: R
authors.initials: R
authors.lastname: Edelson
authors.forename: P
authors.initials: P
authors.lastname: Walsh
authors.forename: D A
authors.initials: DA
authors.lastname: Norris
authors.forename: R C
authors.initials: RC
authors.lastname: Duke
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004249:DNA Damage; D053222:Fas Ligand Protein; D006801:Humans; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008562:Membrane Glycoproteins / Q000502:physiology; D008954:Models, Biological; D009154:Mutation; D011701:PUVA Therapy; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D013312:Stress, Physiological
chemical_list: D000970:Antineoplastic Agents; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor