Functional analysis of a novel DNA polymorphism of a tandem repeated sequence in the asparagine synthetase gene in acute lymphoblastic leukemia cells

Tadayuki Akagi, Dong Yin, Norihiko Kawamata, Claus R Bartram, Wolf-K Hofmann, Jee Hoon Song, Carl W Miller, Monique L den Boer, H Phillip Koeffler

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

Samenvatting

Asparagine synthetase (ASNS) is an enzyme expressed ubiquitously in mammalian cells. Here, we discovered two 14-bp tandem repeat (2R, wild-type) sequences in the first intron of the gene. The 14-bp sequence is similar to the three GC-boxes (GC-I, -II, and -III) found in the promoter region of the ASNS gene, as well as, the binding site of transcription factor Sp-1. Approximately 75% of acute lymphoblastic leukemia (ALL) samples had the 2R sequence in both allele; however, 20% and 3% ALL samples had three (3R) and four (4R) 14-bp tandem repeats in one allele, respectively; the other allele had 2R. The tandem repeat sequence was not specific to the leukemia cells but represents a novel germline polymorphism. Interestingly, the 14-bp sequence functioned as a transcriptional enhancer element as shown by reporter analysis and formed a protein-DNA complex in vitro. Our data for the first time show that the ASNS gene has tandem repeated sequences as a polymorphism, and it can function as a transcriptional element; increased number of tandem repeat producing increased activity. Clinical significance in ALL requires further studies.

Originele taal-2Engels
Pagina's (van-tot)991-6
Aantal pagina's6
TijdschriftLeukemia research
Volume33
Nummer van het tijdschrift7
DOI's
StatusGepubliceerd - jul. 2009
Extern gepubliceerdJa

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