Ectopic expression of a novel CD22 splice-variant regulates survival and proliferation in malignant T cells from cutaneous T cell lymphoma (CTCL) patients.
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Ieva Bagdonaite1,2, Hans H. Wandall2 , Ivan V. Litvinov3, Claudia Nastasi1, Jürgen C. Becker4, Sally Dabelsteen5, Carsten Geisler1, Charlotte M. Bonefeld1, Qian Zhang6, Mariusz A. Wasik6, Youwen Zhou7, Denis Sasseville3, Niels Ødum1 and Anders Woetmann1
1 Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark
2 Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark
3 Division of Dermatology, McGill University Health Centre, Montreal, Quebec, Canada
4 General Dermatology, Medical University of Graz, Austria
5 Department of Oral Medicine and Pathology, School of Dentistry, University of Copenhagen, Copenhagen, Denmark
6 Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, USA
7 Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada
Anders Woetmann, email:
Keywords: CTCL, CD22
Received: February 02, 2015 Accepted: March 03, 2015 Published: March 30, 2015
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 CD22∆N), which lacks the N-terminal domain as demonstrated by exon-specific RT-PCR and differential recognition by anti-CD22 antibodies. Importantly, CD22∆N 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 CD22∆N (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 CD22∆N 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.
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