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Hematopoietic malignancies and gene therapy

机译：造血恶性肿瘤和基因治疗

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摘要

In the case of hematopoietic malignancies, direct approach of gene therapy [gene transfer to cancer cells in order to obtain direct therapeutic effects (cell damage)] is difficult, because malignant cells are distributed in the whole body. As for indirect approaches, immuno-gene-therapy is investigated: As a unique approach, suicide gene therapy is applied to donor lymphocyte infusion for relapsed leukemia after bone marrow transplantation. The purpose of gene therapy is to eliminate donor lymphocytes quickly when severe side effects (GVHD) appeared. HSV-TK gene is generally utilized as a suicide gene. Basic studies are conducted to determine whether anti-tumor-angiogenesis therapy is also effective for hematological malignancies. In addition, leukemia development in 2 patients with X-linked severe combined immunodeficiency who underwent hematopoietic stem cell gene therapy is currently a serious problem in the field of gene therapy. In both cases, LMO2 gene was activated through insertional mutagenesis which was caused by retroviral vectormediated gene transfer. This genetic event is considered to be a trigger of T-lymphocytic leukemia development. Further basic studies are needed in terms of safety for stem cell gene therapy.
机译：在造血恶性肿瘤的情况下，基因治疗的直接方法[基因转移到癌细胞，以获得直接治疗效果（细胞损伤）]是困难的，因为恶性细胞分布在全身中。对于间接方法，研究了免疫基因治疗：作为一种独特的方法，骨髓移植后，自杀基因治疗适用于复发白血病的供体淋巴细胞输注。基因治疗的目的是在出现严重的副作用（GVHD）时快速消除供体淋巴细胞。 HSV-TK基因通常用作自杀基因。进行基础研究以确定抗肿瘤 - 血管生成治疗是否对血液恶性肿瘤同时也有效。此外，2例患有2例患者的白血病发育，X-Catched严重综合免疫缺陷患者接受造血干细胞基因治疗是基因治疗领域的严重问题。在这两种情况下，通过插入诱变激活LMO2基因，这是由逆转录病毒血管术后转移引起的。这种遗传事件被认为是T淋巴细胞白血病发育的触发。在干细胞基因治疗的安全方面需要进一步的基本研究。

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