Bagdonaite Ieva, Wandall Hans H, Litvinov Ivan V, Nastasi Claudia, Becker Jürgen C, Dabelsteen Sally, Geisler Carsten, Bonefeld Charlotte M, Zhang Qian, Wasik Mariusz A, Zhou Youwen, Sasseville Denis, Ødum Niels, Woetmann Anders
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.
Oncotarget. 2015 Jun 10;6(16):14374-84. doi: 10.18632/oncotarget.3720.
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.
CD22是唾液酸结合免疫球蛋白样凝集素（Siglec）家族的成员之一，据描述仅存在于B淋巴细胞和B细胞来源的肿瘤中。在此，我们描述了一种新型的CD22剪接形式（命名为CD22ΔN），外显子特异性逆转录聚合酶链反应（RT-PCR）和抗CD22抗体的差异识别表明其缺乏N端结构域。重要的是，60例皮肤T细胞淋巴瘤（CTCL）患者中有39例的皮肤病变中表达CD22ΔN mRNA，而很少有患者（60例中的6例）表达全长野生型CD22（CD22wt）。此外，肿瘤活检的免疫组化染色证实CD22在CD4+ T细胞中表达。而且，4株恶性T细胞系中有4株表达CD22：2株细胞系表达CD22ΔN（MyLa2059和PB2B），2株表达CD22wt（MAC-1和MAC-2A）。小干扰RNA（siRNA）介导的CD22沉默损害恶性T细胞的增殖和存活，表明CD22ΔN和CD22wt在这些细胞中具有功能作用。总之，我们首次提供了CD22异位表达以及一种新型剪接变体调节CTCL中恶性增殖和存活的证据。分析CD22在皮肤淋巴瘤中的表达和功能可能为开发针对我们患者的新型靶向治疗奠定基础。
