Roncador Giovanna, Puñet-Ortiz Joan, Maestre Lorena, Rodríguez-Lobato Luis Gerardo, Jiménez Scherezade, Reyes-García Ana Isabel, García-González Álvaro, García Juan F, Piris Miguel Ángel, Montes-Moreno Santiago, Rodríguez-Justo Manuel, Mena Mari-Pau, Fernández de Larrea Carlos, Engel Pablo
Monoclonal Antibodies Unit, Biotechnology Program, Spanish National Cancer Centre (CNIO), Centro de Investigación Médica en red Cancer (CIBERONC), 28029 Madrid, Spain.
Immunology Unit, Department of Biomedical Sciences, Faculty of Medicine and Medical Sciences, University of Barcelona, Casanova 172, 08036 Barcelona, Spain.
Cancers (Basel). 2022 Apr 26;14(9):2154. doi: 10.3390/cancers14092154.
CD229 (Ly9) homophilic receptor, which belongs to the SLAM family of cell-surface molecules, is predominantly expressed on B and T cells. It acts as a signaling molecule, regulating lymphocyte homoeostasis and activation. Studies of CD229 function indicate that this receptor functions as a regulator of the development of marginal-zone B cells and other innate-like T and B lymphocytes. The expression on leukemias and lymphomas remains poorly understood due to the lack of CD229 monoclonal antibodies (mAb) for immunohistochemistry application (IHC). In this study, we used a new mAb against the cytoplasmic region of CD229 to study the expression of CD229 on normal tissues and B-cell malignancies, including multiple myeloma (MM), using tissue microarrays. We showed CD229 to be restricted to hematopoietic cells. It was strongly expressed in all cases of MM and in most marginal-zone lymphomas (MZL). Moderate CD229 expression was also found in chronic lymphocyte leukemia (CLL), follicular (FL), classic mantle-cell (MCL) and diffuse large B-cell lymphoma. Given the high expression on myeloma cells, we also analyzed for the presence of soluble CD229 in the sera of these patients. Serum levels of soluble CD229 (sCD229) at the time of diagnosis in MM patients could be useful as a prognostic biomarker. In conclusion, our results indicate that CD229 represents not only a useful biomarker but also an attractive therapeutic target.
CD229（Ly9）同源受体属于细胞表面分子的信号淋巴细胞激活分子相关受体（SLAM）家族，主要在B细胞和T细胞上表达。它作为一种信号分子，调节淋巴细胞的稳态和激活。对CD229功能的研究表明，该受体作为边缘区B细胞以及其他固有样T和B淋巴细胞发育的调节因子发挥作用。由于缺乏用于免疫组织化学应用（IHC）的CD229单克隆抗体（mAb），目前对白血病和淋巴瘤中CD229表达的了解仍然很少。在本研究中，我们使用了一种针对CD229胞质区域的新型单克隆抗体，通过组织芯片研究CD229在正常组织和B细胞恶性肿瘤（包括多发性骨髓瘤（MM））中的表达。我们发现CD229仅限于造血细胞。它在所有MM病例和大多数边缘区淋巴瘤（MZL）中均强烈表达。在慢性淋巴细胞白血病（CLL）、滤泡性淋巴瘤（FL）、经典套细胞淋巴瘤（MCL）和弥漫性大B细胞淋巴瘤中也发现了中等水平的CD229表达。鉴于骨髓瘤细胞上的高表达，我们还分析了这些患者血清中可溶性CD229的存在情况。MM患者诊断时血清可溶性CD229（sCD229）水平可能作为一种预后生物标志物。总之，我们的结果表明，CD229不仅是一种有用的生物标志物，也是一个有吸引力的治疗靶点。
