Brenner M K
Cell and Gene Therapy Program, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, U.S.A.
J Pediatr Hematol Oncol. 1997 Jan-Feb;19(1):1-6. doi: 10.1097/00043426-199701000-00001.
Originally conceived as a means to replace or correct defective genes in patients with inherited disorders, gene transfer has shown broad potential for medical intervention in the hematopoietic cancers and for study of hematopoietic stem cell biology. The purpose of this article is to review emerging applications of gene therapy with special reference to hematopoietic neoplasia.
Gene transfer strategies now under investigation in the hematopoietic cancers focus on (a) repair of one or more genetic defects associated with the malignant process, (b) delivery of a prodrug-metabolizing enzyme that causes tumor cells to become sensitive to the corresponding anticancer drug, (c) modification of immune responses to the cancer, or (d) introduction of drug resistance genes to increase the therapeutic index of cytotoxic agents. Finally, by marking normal or malignant cells with readily detectable genes, one can monitor the efficacy of therapy or study the dynamics of stem cell behavior in vivo.
Despite their undisputed contributions to our knowledge of the hematopoietic cancers, gene transfer studies have been limited by the quality of vector technologies. As transduction efficiencies and gene regulatory mechanisms improve, gene transfer can be expected to evolve into a major therapeutic modality in its own right.
基因转移最初被设想为一种替代或纠正遗传性疾病患者缺陷基因的手段，现已显示出在造血系统癌症的医学干预及造血干细胞生物学研究方面具有广泛潜力。本文旨在特别针对造血系统肿瘤，综述基因治疗的新兴应用。
目前在造血系统癌症中正在研究的基因转移策略集中于：（a）修复与恶性过程相关的一个或多个遗传缺陷；（b）递送一种前药代谢酶，使肿瘤细胞对相应抗癌药物敏感；（c）改变对癌症的免疫反应；或（d）引入耐药基因以提高细胞毒性药物的治疗指数。最后，通过用易于检测的基因标记正常或恶性细胞，可以监测治疗效果或研究体内干细胞行为的动态变化。
尽管基因转移研究对我们了解造血系统癌症做出了无可争议的贡献，但一直受到载体技术质量的限制。随着转导效率和基因调控机制的改善，基因转移有望自身发展成为一种主要的治疗方式。
