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

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)991-6
Number of pages6
JournalLeukemia research
Volume33
Issue number7
DOIs
Publication statusPublished - Jul 2009
Externally publishedYes

Keywords

  • Aspartate-Ammonia Ligase/genetics
  • Base Sequence
  • DNA, Neoplasm/genetics
  • Electrophoretic Mobility Shift Assay
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Molecular Sequence Data
  • Polymorphism, Genetic/genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma/enzymology
  • Promoter Regions, Genetic/genetics
  • RNA, Messenger/genetics
  • Sequence Homology, Nucleic Acid
  • Tandem Repeat Sequences/genetics
  • Tumor Cells, Cultured

Fingerprint

Dive into the research topics of 'Functional analysis of a novel DNA polymorphism of a tandem repeated sequence in the asparagine synthetase gene in acute lymphoblastic leukemia cells'. Together they form a unique fingerprint.

Cite this