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Identification of a gene element essential for leukemia-specific expression of transgenes.

Abstract：

:Leukemia-specific promoters and enhancers for gene therapy had never been reported. Since the Wilms' tumor gene WT1 is overexpressed in almost all types of leukemia, WT1 is an ideal target of leukemia-specific therapy. To explore the possibility of gene therapy for leukemia using WT1 promoter and enhancer, their activities in several kinds of cells were analyzed by using the enhanced green fluorescent protein (EGFP) gene as a reporter. First, we identified the best combination (654P/EGFP/int3- enh/3'-enh vector) of the 654-bp WT1 promoter and the two WT1 enhancers located in intron 3 and at the 3' end of the WT1 gene for inducing EGFP expression in K562 cells, which endogenously expressed WT1. When this was transfected into WT1-expressing leukemia cells (K562, HEL), WT1-nonexpressing hematopoietic cells (Daudi, U937), and WT1-expressing nonhematopoietic cells (TYK-nu-CPr, SW480, 293 T), 19.8, 22.9, 1.47, 1.43, 4.50, 4.16, and 1.09 times EGFP expression was induced, respectively, compared to that by the promoter-less EGFP vector. These results showed that the 654P/EGFP/int3-enh/3'-enh vector specifically induced high levels of EGFP expression in WT1-expressing leukemia cells. 654P/int3- enh/3'-enh vector containing transgenes such as suicide genes might become useful tools for leukemia-specific gene therapy.

journal_name

Leukemia

journal_title

Leukemia

authors

Hosen N,Yanagihara M,Nakazawa T,Kanato K,Nishida S,Shirakata T,Asada M,Masuda T,Taniguchi Y,Kawakami M,Tsuboi A,Ikegame K,Oka Y,Ogawa H,Kawase I,Oji Y,Sugiyama H

doi

10.1038/sj.leu.2403260

subject

Has Abstract

pub_date

2004-03-01 00:00:00

pages

415-9

issue

3

eissn

0887-6924

issn

1476-5551

pii

2403260

journal_volume

18

pub_type

杂志文章

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