Ectopic expression of a novel CD22 splice-variant regulates survival and proliferation in malignant T cells from cutaneous T cell lymphoma (CTCL) patients

TY - JOUR

T1 - Ectopic expression of a novel CD22 splice-variant regulates survival and proliferation in malignant T cells from cutaneous T cell lymphoma (CTCL) patients

AU - Bagdonaite, Ieva

AU - Wandall, Hans H

AU - Litvinov, Ivan V

AU - Nastasi, Claudia

AU - Becker, Jürgen C

AU - Dabelsteen, Sally

AU - Geisler, Carsten

AU - Bonefeld, Charlotte M

AU - Zhang, Qian

AU - Wasik, Mariusz A

AU - Zhou, Youwen

AU - Sasseville, Denis

AU - Ødum, Niels

AU - Woetmann, Anders

PY - 2015/6/10

Y1 - 2015/6/10

N2 - 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 CD22δN), which lacks the N-terminal domain as demonstrated by exon-specific RT-PCR and differential recognition by anti-CD22 antibodies. Importantly, CD22δN 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 CD22δN (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 CD22δN 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.

AB - 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 CD22δN), which lacks the N-terminal domain as demonstrated by exon-specific RT-PCR and differential recognition by anti-CD22 antibodies. Importantly, CD22δN 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 CD22δN (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 CD22δN 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.

UR - http://www.ncbi.nlm.nih.gov.ep.fjernadgang.kb.dk/pmc/articles/PMC4546473/

U2 - 10.18632/oncotarget.3720

DO - 10.18632/oncotarget.3720

M3 - Journal article

C2 - 25957418

SN - 1949-2553

VL - 6

SP - 14374

EP - 14384

JO - Oncotarget

JF - Oncotarget

IS - 16

ER -