title: The importance of Notch signaling in peripheral T-cell lymphomas.
abstract: Peripheral T-cell lymphomas (PTLs) represent an area of high medical need. Previously, we demonstrated high expression of Notch, a known oncogene, in primary cutaneous anaplastic large cell lymphoma (ALCL). In this study, we performed immunohistochemical staining for Notch1 in lymph nodes from PTL not otherwise specified (PTL-NOS) and systemic ALCL (ALK+ and ALK-) and report a similar distribution among the three subgroups: Negative, moderate and strong expression was, respectively, 18%, 27% and 55% for PTL-NOS (33 cases), 20%, 0% and 80% for ALCL ALK+ (10 cases) and 45%, 22% and 33% for ALCL ALK- (nine cases) (p > 0.05). In the ALK+ ALCL cell line, Karpas-299, pharmacological inhibition of Notch with γ-secretase inhibitor (GSI) I was far more potent than with GSI IX, XX and XXI with regard to cell viability and apoptosis. In conclusion, PTL tumor cells have prominent Notch1 expression and treatment with Notch inhibitors has cytotoxic effects.
authors.affiliation: Department of Dermatology, Bispebjerg Hospital, University of Copenhagen , Denmark.
authors.forename: Maria Rørbæk
authors.initials: MR
authors.lastname: Kamstrup
authors.forename: Edyta
authors.initials: E
authors.lastname: Biskup
authors.forename: Lise Mette Rahbek
authors.initials: LM
authors.lastname: Gjerdrum
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ralfkiaer
authors.forename: Omid
authors.initials: O
authors.lastname: Niazi
authors.forename: Robert
authors.initials: R
authors.lastname: Gniadecki
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D016411:Lymphoma, T-Cell, Peripheral / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000494:pharmacology; D051881:Receptor, Notch1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051880:Receptors, Notch / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D055815:Young Adult
chemical_list: D009842:Oligopeptides; D051881:Receptor, Notch1; D051880:Receptors, Notch; C523462:benzyloxycarbonyl-leucyl-leucyl-norleucinal; D053829:Amyloid Precursor Protein Secretases