Blood:VEGF,急性淋巴细胞白血病侵入中枢神经系统的新机制

2017-06-01 fengxiangxin MedSci原创

在急性淋巴细胞白血病中,中枢神经系统受累是临床关注的重点。尽管在很多病例中没有检测出中枢神经系统受累,但是对于无复发的幸存者,鞘内注射防治中枢神经系统白血病是必需的。这说明在大部分病人中存在难以构成诊断的亚临床表现

在急性淋巴细胞白血病中,中枢神经系统受累是临床关注的重点。尽管在很多病例中没有检测出中枢神经系统受累,但是对于无复发的幸存者,鞘内注射防治中枢神经系统白血病是必需的。这说明在大部分病人中存在难以构成诊断的亚临床表现。然而,中枢神经系统定向治疗与神经认知功能障碍和继发性肿瘤等长期后遗症相关。因此,为了更好的预防和治疗CNS白血病,需要更好的理解和认识ALL细胞侵入CNS的分子机制和途径。

当研究者把原代ALL细胞移植到NOD/SCID小鼠后,很好的复制了ALL脑膜浸润病人的临床和组织病理学特征。进入中枢神经系统并浸润脑膜的ALL细胞特征性高表达血管内皮生长因子A,VEGF调节了ALL细胞在CNS血管内皮的跨内皮迁移,而与细胞活力、生长、增殖以及存活均没有联系。抗VEGF药物贝伐单抗在体内的捕获试验进一步证明了VEGF在介导ALL细胞侵入CNS以及脑膜浸润中的重要性 。

因此,确定了ALL细胞侵入CNS的一个机制,靶向控制VEGF介导ALL细胞侵入CNS的信号通路有望代替传统的中枢神经系统鞘内注射成为控制CNS白血病的新策略。

原始出处:

Munch, V., et al., Central Nervous System Involvement in Acute Lymphoblastic Leukemia Is Mediated by Vascular Endothelial Growth Factor. Blood,2017 May 26. pii: blood-2017-03-769315. doi: 10.1182/blood-2017-03-769315.

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