Planelles Lourdes, Carvalho-Pinto Carla E, Hardenberg Gijs, Smaniotto Salette, Savino Wilson, Gómez-Caro Ruth, Alvarez-Mon Melchor, de Jong Joan, Eldering Eric, Martínez-A Carlos, Medema Jan Paul, Hahne Michael
Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, UAM Campus Cantoblanco, E-28049 Madrid, Spain.
Cancer Cell. 2004 Oct;6(4):399-408. doi: 10.1016/j.ccr.2004.08.033.
A tumor-supporting role for the TNF-like ligand APRIL has been suggested. Here we describe that 9- to 12-month-old APRIL transgenic mice develop lymphoid tumors that originate from expansion of the peritoneal B-1 B cell population. Aging APRIL transgenic mice develop progressive hyperplasia in mesenteric lymph nodes and Peyer's patches, disorganization of affected lymphoid tissues, mucosal and capsular infiltration, and eventual tumor cell infiltration into nonlymphoid tissues such as kidney and liver. We detected significantly increased APRIL levels in sera of B cell chronic lymphoid leukemia (B-CLL) patients, indicating that APRIL promotes onset of B-1-associated neoplasms and that APRIL antagonism may provide a therapeutic strategy to treat B-CLL patients.
已有研究表明,肿瘤坏死因子样配体APRIL具有支持肿瘤生长的作用。在此,我们描述了9至12月龄的APRIL转基因小鼠会发生淋巴样肿瘤,这些肿瘤起源于腹膜B-1 B细胞群体的扩增。衰老的APRIL转基因小鼠在肠系膜淋巴结和派尔集合淋巴结中出现进行性增生,受影响的淋巴组织结构紊乱,黏膜和包膜浸润,最终肿瘤细胞浸润到肾脏和肝脏等非淋巴组织。我们检测到B细胞慢性淋巴细胞白血病(B-CLL)患者血清中的APRIL水平显著升高,这表明APRIL促进了与B-1相关肿瘤的发生,并且拮抗APRIL可能为治疗B-CLL患者提供一种治疗策略。