title: Psoralen with ultraviolet A-induced apoptosis of cutaneous lymphoma cell lines is augmented by type I interferons via the JAK1-STAT1 pathway.
abstract: BACKGROUND
  Photochemotherapy with psoralen and ultraviolet A (PUVA), with or without adjuvant interferon-α (IFN-α), is a first-line therapy for early-stage mycosis fungoides and other forms of cutaneous T-cell lymphoma (CTCL). However, the mechanism by which PUVA with IFN-α work in CTCL is poorly understood.
  
  
  OBJECTIVE
  To develop a model to investigate the mechanisms of PUVA and PUVA with IFN-α in CTCL cells.
  
  
  METHODS
  An in vitro model to study the molecular mechanisms of PUVA was created using two different CTCL cell lines, MyLa, which has functional p53, and HuT-78, in which p53 is inactivated due to a homozygous nonsense mutation.
  
  
  RESULTS
  PUVA caused G2/M cell cycle block and apoptosis of MyLa and HuT-78 accompanied by increase in the expression of the mitochondrial pro-apoptotic genes Bax, BAK, and PUMA and a downregulation in anti-apoptotic Bcl-2. p53 was induced and c-Myc was repressed by PUVA, but neither were essential for PUVA-induced apoptosis. IFN-α augmented PUVA-induced apoptosis via the JAK1 pathway, and this activity could be inhibited by ruxolitinib.
  
  
  CONCLUSIONS
  PUVA induces p53-independent apoptosis in CTCL cell lines, and this process is augmented by type I interferons via the JAK1 pathway.
authors.affiliation: Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark.
authors.forename: Walter
authors.initials: W
authors.lastname: Liszewski
authors.affiliation: Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark.
authors.forename: David Gram
authors.initials: DG
authors.lastname: Naym
authors.affiliation: Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark.
authors.forename: Edyta
authors.initials: E
authors.lastname: Biskup
authors.affiliation: Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark.|Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.|Division of Dermatology, University of Alberta, Edmonton, AB, Canada.
authors.forename: Robert
authors.identifier: http://orcid.org/0000-0002-2310-8300
authors.initials: R
authors.lastname: Gniadecki
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects / Q000528:radiation effects; D015870:Gene Expression; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D053613:Janus Kinase 1 / Q000378:metabolism; D000075242:Janus Kinase Inhibitors / Q000494:pharmacology; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D059566:M Phase Cell Cycle Checkpoints / Q000528:radiation effects; D009570:Nitriles; D011701:PUVA Therapy; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C494772:BAK1 protein, human; C494826:BAX protein, human; C438378:BBC3 protein, human; C000595707:BCL2 protein, human; D016898:Interferon-alpha; D000075242:Janus Kinase Inhibitors; D009570:Nitriles; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D011720:Pyrazoles; D011743:Pyrimidines; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D016159:Tumor Suppressor Protein p53; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; C540383:ruxolitinib; C507904:JAK1 protein, human; D053613:Janus Kinase 1
keywords: JAK; apoptosis; cutaneous lymphoma; interferons; psoralen with ultraviolet A