title: Apoptosis Induction and Gene Expression Profile Alterations of Cutaneous T-Cell Lymphoma Cells following Their Exposure to Bortezomib and Methotrexate.
abstract: Mycosis fungoides (MF) and its leukemic variant Sézary syndrome (SS) comprise the majority of CTCL, a heterogenous group of non-Hodgkins lymphomas involving the skin. The CTCL's resistance to chemotherapy and the lack of full understanding of their pathogenesis request further investigation. With the view of a more targeted therapy, we evaluated in vitro the effectiveness of bortezomib and methotrexate, as well as their combination in CTCL cell lines, regarding apoptosis induction. Our data are of clinical value and indicate that the bortezomib/methotrexate combinational therapy has an inferior impact on the apoptosis of CTCL compared to monotherapy, with bortezomib presenting as the most efficient treatment option for SS and methotrexate for MF. Using PCR arrays technology, we also investigated the alterations in the expression profile of genes related to DNA repair pathways in CTCL cell lines after treatment with bortezomib or methotrexate. We found that both agents, but mostly bortezomib, significantly deregulate a large number of genes in SS and MF cell lines, suggesting another pathway through which these agents could induce apoptosis in CTCL. Finally, we show that SS and MF respond differently to treatment, verifying their distinct nature and further emphasizing the need for discrete treatment approaches.
authors.affiliation: Second Dept. of Internal Medicine and Research Institute, Attikon University General Hospital, Rimini 1, Haidari, Athens, Greece.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Mpakou
authors.affiliation: Second Department of Dermatology, Attikon University General Hospital, Rimini 1, Haidari, Athens, Greece.|First Department of Dermatology, A. Syggros University Hospital, Athens University, Medical School, Greece.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Papadavid
authors.affiliation: Second Dept. of Internal Medicine and Research Institute, Attikon University General Hospital, Rimini 1, Haidari, Athens, Greece.
authors.forename: Frieda
authors.initials: F
authors.lastname: Kontsioti
authors.affiliation: Second Dept. of Internal Medicine and Research Institute, Attikon University General Hospital, Rimini 1, Haidari, Athens, Greece.
authors.forename: Eugene
authors.initials: E
authors.lastname: Konsta
authors.affiliation: Second Dept. of Internal Medicine and Research Institute, Attikon University General Hospital, Rimini 1, Haidari, Athens, Greece.
authors.forename: Miriam
authors.initials: M
authors.lastname: Vikentiou
authors.affiliation: Department of Cytopathology, Attikon University General Hospital, Athens, Greece.
authors.forename: Aris
authors.initials: A
authors.lastname: Spathis
authors.affiliation: Second Dept. of Internal Medicine and Research Institute, Attikon University General Hospital, Rimini 1, Haidari, Athens, Greece.
authors.forename: Sotiris
authors.initials: S
authors.lastname: Papageorgiou
authors.affiliation: Second Dept. of Internal Medicine and Research Institute, Attikon University General Hospital, Rimini 1, Haidari, Athens, Greece.
authors.forename: Diamantina
authors.initials: D
authors.lastname: Vasilatou
authors.affiliation: Second Dept. of Internal Medicine and Research Institute, Attikon University General Hospital, Rimini 1, Haidari, Athens, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Gkontopoulos
authors.affiliation: Second Dept. of Internal Medicine and Research Institute, Attikon University General Hospital, Rimini 1, Haidari, Athens, Greece.
authors.forename: Efthimia
authors.initials: E
authors.lastname: Mpazani
authors.affiliation: Department of Cytopathology, Attikon University General Hospital, Athens, Greece.
authors.forename: Petros
authors.initials: P
authors.lastname: Karakitsos
authors.affiliation: Second Department of Dermatology, Attikon University General Hospital, Rimini 1, Haidari, Athens, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Rigopoulos
authors.affiliation: Second Dept. of Internal Medicine and Research Institute, Attikon University General Hospital, Rimini 1, Haidari, Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Dimitriadis
authors.affiliation: Second Dept. of Internal Medicine and Research Institute, Attikon University General Hospital, Rimini 1, Haidari, Athens, Greece.
authors.forename: Vasiliki
authors.identifier: http://orcid.org/0000-0003-0421-9424
authors.initials: V
authors.lastname: Pappa
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000069286:Bortezomib / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004260:DNA Repair; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D016410:Lymphoma, T-Cell, Cutaneous / Q000235:genetics / Q000473:pathology*; D008727:Methotrexate / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D000069286:Bortezomib; D008727:Methotrexate