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M Fujita, K Murata and H Shiku
Department of Oncology, Nagasaki University School of Medicine, Japan.
Adult T-cell leukemia (ATL), a disorder associated with high mortality
rates, arises from human T-lymphotropic virus type I (HTLV-I)-infected CD4+
T cells. We designed a retroviral vector-based gene therapy approach to
ATL. The long terminal repeat (LTR) of HTLV-I is transactivated by the
viral tax protein. We constructed a hybrid gene consisting of herpes
simplex virus thymidine kinase (HSV TK) under the control of the HTLV-I LTR
and inserted it into a retroviral vector. When HTLV-I-transformed and
tax-expressing human T-cell lines were infected with this recombinant
retrovirus (LNLTK alpha virus), they expressed high levels of HSV TK and
exhibited increased sensitivity to acyclovir, a nucleoside analog that is
converted to the toxic anabolite after phosphorylation by the HSV TK. On
the other hand, the retroviral infection had little effect on
acyclovir-induced cytotoxicity in HTLV-I- negative human hematopoietic cell
lines. Our data may provide the prospect of the gene therapy for ATL by
tax-targeted selective elimination of leukemic cells.
This article has been cited by other articles:
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| Copyright © 1994 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||