[Hematopoietic malignancies and gene therapy].
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.
Division of Hematology, Dept. of Medicine, Jichi Medical School.
Keiya
K
Ozawa
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins / Q000235:genetics; D015316:Genetic Therapy / Q000639:trends; D005822:Genetic Vectors; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D060588:LIM Domain Proteins; D007938:Leukemia / Q000209:etiology; D008667:Metalloproteins / Q000235:genetics; D011518:Proto-Oncogene Proteins; D016511:Severe Combined Immunodeficiency / Q000628:therapy; D018139:Simplexvirus; D013937:Thymidine Kinase / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C085117:LMO2 protein, human; D008667:Metalloproteins; D011518:Proto-Oncogene Proteins; D013937:Thymidine Kinase