Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING
JIB
GLOBETECH PUBLISHING

Shutting Down Multiple DNA Synthesis Pathways Cures Leukemia in Mouse Model

By BiotechDaily International staff writers
Posted on 10 Mar 2014
Image: The number of leukemia cells (red) was greatly reduced in treated (right) vs. untreated (left) mice while sparing any significant damage to normal blood cells (black) (Photo courtesy of the Rockefeller University Press).
Image: The number of leukemia cells (red) was greatly reduced in treated (right) vs. untreated (left) mice while sparing any significant damage to normal blood cells (black) (Photo courtesy of the Rockefeller University Press).
Drug treatment that combined inhibitors of both the de novo (DNP) and salvage (NSP) pathways for DNA synthesis cured acute lymphoblastic leukemia (ALL) in a mouse model of the disease.

Investigators at the University of California, Los Angeles (USA) blocked the DNP synthesis of DNA by treating ALL mice with thymidine. This treatment was not sufficient to prevent growth of cancer cells, which switched to the NSP pathway.

To block the NSP pathway the investigators administered DI-39, a new high affinity small-molecule inhibitor of the rate-limiting enzyme DC kinase (DCK). DCK is required for the phosphorylation of several deoxyribonucleosides and their nucleoside analogs. Deficiency of DCK is associated with resistance to antiviral and anticancer chemotherapeutic agents. Conversely, increased DCK activity is associated with increased activation of these compounds to cytotoxic nucleoside triphosphate derivatives. DCK is clinically important because of its relationship to drug resistance and sensitivity.

The investigators reported in the February 24, 2014, online edition of the Journal of Experimental Medicine that a therapeutic regimen that simultaneously co-targeted the DNP pathway with thymidine and the NSP pathway with DI-39 was effective against ALL models in mice, without detectable host toxicity.

"This new dual targeting approach shows that we can overcome the redundancy in DNA synthesis in ALL cells and identifies a potential target for metabolic intervention in ALL, and possibly in other hematological cancers," said senior author Dr. Caius Radu, associate professor of molecular and medical pharmacology at the University of California, Los Angeles. "This interdisciplinary study not only advances our understanding of DNA synthesis in leukemic cells but also identifies targeted metabolic intervention as a new therapeutic approach in ALL. Clinical trials will be required to establish whether these promising findings will translate into a new therapeutic approach for ALL."

Related Links:

University of California, Los Angeles



comments powered by Disqus

Channels

Genomics/Proteomics

view channel
Image: This micrograph depicts the presence of aerobic Gram-negative Neisseria meningitidis diplococcal bacteria; magnification 1150x (Photo courtesy of the CDC - US Centers for Disease Control and Prevention).

Infection by Meningitis Bacteria Depends on Dimerization State of Certain Host Cell Proteins

A team of molecular microbiologists has untangled the complex three-way interaction between the non-integrin laminin receptor (LAMR1), galectin-3 (Gal-2), and the pathogenic bacterium Neisseria meningitidis.... Read more

Lab Technologies

view channel
Image: The UC Santa Cruz Ebola Genome Portal contains links to the newly created Ebola browser and to scientific literature on the deadly virus (Photo courtesy of UCSC).

Ebola Genome Browser Now Online to Help Scientists’ Respond to Crisis

A US genomics institute has just released a new Ebola genome browser to help international researchers develop a vaccine and antiserum to help stop the spread of the Ebolavirus. The investigators led... Read more

Business

view channel

Interest in Commercial Applications for Proteomics Continues to Grow

Increasing interest in the field of proteomics has led to a series of agreements between private proteomic companies and academic institutions as well as deals between pharmaceutical companies and novel proteomics innovator biotech companies. Proteomics is the study of the structure and function of proteins.... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.