title: Ectopic expression of a novel CD22 splice-variant regulates survival and proliferation in malignant T cells from cutaneous T cell lymphoma (CTCL) patients.
abstract: CD22 is a member of the Sialic acid-binding Ig-like lectin (Siglec) family of lectins described to be exclusively present in B lymphocytes and B cell-derived neoplasms. Here, we describe a novel splice form of CD22 (designated CD22âN), which lacks the N-terminal domain as demonstrated by exon-specific RT-PCR and differential recognition by anti-CD22 antibodies. Importantly, CD22âN mRNA is expressed in skin lesions from 39 out of 60 patients with cutaneous T cell lymphoma (CTCL), whereas few patients (6 out of 60) expresses full-length, wild type CD22 (CD22wt). In addition, IHC staining of tumor biopsies confirmed the expression of CD22 in CD4+ T cells. Moreover, four out of four malignant T cell lines express CD22: Two cell lines express CD22âN (MyLa2059 and PB2B) and two express CD22wt (MAC-1 and MAC-2A). siRNA-mediated silencing of CD22 impairs proliferation and survival of malignant T cells, demonstrating a functional role for both CD22âN and CD22wt in these cells.In conclusion, we provide the first evidence for an ectopic expression of CD22 and a novel splice variant regulating malignant proliferation and survival in CTCL. Analysis of expression and function of CD22 in cutaneous lymphomas may form the basis for development of novel targeted therapies for our patients.
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.|Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ieva
authors.initials: I
authors.lastname: Bagdonaite
authors.affiliation: Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Hans H
authors.initials: HH
authors.lastname: Wandall
authors.affiliation: Division of Dermatology, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Ivan V
authors.initials: IV
authors.lastname: Litvinov
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Claudia
authors.initials: C
authors.lastname: Nastasi
authors.affiliation: General Dermatology, Medical University of Graz, Graz, Austria.
authors.forename: Jürgen C
authors.initials: JC
authors.lastname: Becker
authors.affiliation: Department of Oral Medicine and Pathology, School of Dentistry, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Sally
authors.initials: S
authors.lastname: Dabelsteen
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Carsten
authors.initials: C
authors.lastname: Geisler
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Bonefeld
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, USA.
authors.forename: Mariusz A
authors.initials: MA
authors.lastname: Wasik
authors.affiliation: Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Youwen
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Division of Dermatology, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Denis
authors.initials: D
authors.lastname: Sasseville
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Ødum
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Woetmann
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D008213:Lymphocyte Activation; D016410:Lymphoma, T-Cell, Cutaneous / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D020033:Protein Isoforms; D012326:RNA Splicing; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000096:biosynthesis* / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014162:Transfection
chemical_list: C497867:CD22 protein, human; D020033:Protein Isoforms; D051918:Sialic Acid Binding Ig-like Lectin 2
keywords: CD22; CTCL