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Method for the Direct Detection and Quantitation of Asparagine Synthetase in Biological Samples

Description of Invention:
Acute lymphoblastic leukemia (ALL) is a fast-growing cancer that targets immature cells of the blood and bone marrow. Clinical treatments of ALL use enzyme-based methods, such as L-asparaginase (ASNase), for depletion of cellular asparagine in combination with standard chemotherapeutic agents. Although ASNase can be used to treat both childhood and adult forms of ALL, its use is limited because patients can often develop resistance to ASNase therapy. Studies have shown a correlation between ASNase resistance and increased expression levels of asparaginase synthetase (ASNS) enzyme, which catalyzes the biosynthesis of cellular L-asparagine from L-aspartate in an ATP-dependent reaction. At present, measurement of ASNS expression levels are based on mRNA or antibody based assays; however, these methods are not suitable for direct quantitation of protein in biological samples. Thus, new and improved methods that directly measure ASNS protein levels are needed.

Researchers at the NCI have developed novel methods for quantitating ASNS protein in biological samples using isotope-labeled standard peptides and mass spectrometry. The current technology describes methods of identifying a patient with cancer or chemoresistant cancer, monitoring the treatment regimen of a patient with cancer, as well as methods for detecting modulators and their ability to affect ASNS expression levels. Further described are novel pharmaceutical compositions with potential use as chemotherapeutic agents.

Applications:
  • Diagnostic assay for leukemia or chemoresistant cancer
  • Use in screening or identifying potential chemotherapeutic agents
  • Use in measuring a patient’s sensitivity to ASNase therapy
Market:
  • Approximately 5,200 people are diagnosed with ALL each year in the United States
  • ALL is the most common type of cancer in children in developed countries
Development Status:
Early stage

Inventors:
Thomas P. Conrads (NCI/SAIC) et al.

Patent Status:
DHHS Reference No. E-189-2006/0 --
International Application No. PCT/US06/28965 filed 25 Jul 2006

Licensing Status:
This technology is no longer available for licensing.


Portfolios:
Cancer

Cancer -Therapeutics-Conventional Chemotherapy-Other
Cancer -Therapeutics


For Additional Information Please Contact:
John Stansberry Ph.D.
NIH Office of Technology Transfer
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: (301)435-5236
Email: stansbej@mail.nih.gov
Fax: (301) 402-0220


Web Ref: 1565

Updated: 6/07

 

 
 
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