Kang Elizabeth M, Tisdale John F
Molecular and Clinical Hematology Branch, National Institutes of Diabetes and Digestive and Kidney Disorders, National Institutes of Health, Building 10, Room 9N116, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Curr Hematol Rep. 2004 Jul;3(4):274-81.
Hematopoietic stem cell gene transfer using integrating vectors has been actively investigated for more than two decades as a prospective treatment for several congenital and acquired human diseases, and retroviral vectors encoding potentially therapeutic genes have been the most rigorously pursued. Early trials in humans testing retroviral vectors in several clinical settings supported the safety of this approach, and recent studies have demonstrated remarkable efficacy in children with severe combined immunodeficiency. The anticipated success established the therapeutic potential of hematopoietic stem cell gene transfer, but the subsequent development of leukemia in two treated children has re-emphasized the risks related to gene therapy. In this review, we describe this complication, discuss the leukemogenic risk of integrating retroviral vectors, and propose strategies to decrease the likelihood of its occurrence.
二十多年来，使用整合载体进行造血干细胞基因转移作为几种先天性和后天性人类疾病的一种前瞻性治疗方法一直受到积极研究，编码潜在治疗基因的逆转录病毒载体一直是研究最为深入的。在几种临床环境中测试逆转录病毒载体的早期人体试验支持了这种方法的安全性，最近的研究表明其在重症联合免疫缺陷儿童中具有显著疗效。预期的成功确立了造血干细胞基因转移的治疗潜力，但两名接受治疗的儿童随后发生白血病再次强调了基因治疗相关的风险。在这篇综述中，我们描述了这种并发症，讨论了整合逆转录病毒载体的致白血病风险，并提出降低其发生可能性的策略。
