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JCI table of contents -- March 22, 2007

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ONCOLOGY: Leukemic cells find protection in the bone marrow from anticancer drug

As part of their therapeutic regimen, individuals with acute lymphoblastic leukemia (ALL) are treated with asparaginase a protein that breaks down the amino acid asparagine. ALL cells are sensitive to a lack of asparagine in their environment because they express very low levels of the protein ASNS, which makes asparagine. However, the mechanisms regulating the susceptibility of ALL cells to asparaginase are not completely clear, as ASNS expression levels do not always correlate with clinical effectiveness of the treatment.

In a study that appears online on March 22 in advance of publication in the April print issue of the Journal of Clinical Investigation, Dario Campana and colleagues from St. Jude Childrens Research Hospital, Memphis, show that in vitro, mesenchymal cells (MSCs) from the bone marrow which is where ALL cells grow in patients can provide high levels of asparagine to ALL cells, enabling them to overcome the effects of asparaginse. Protection correlated with the level of ASNS expressed by the MSCs; decreased ASNS expression reduced the ability of MSCs to protect ALL cells from asparaginase, whereas enhanced expression increased their protective capacity. This study indicates that MSCs in the bone marrow can provide protective niches for ALL cells and leads to the suggestion that ASNS in MSCs might be a good target for the treatment of individuals with ALL.

TITLE: Mesenchymal cells regulate the response of acute lymphoblastic cells to asparaginase

AUTHOR CONTACT:
Dario Campana
St. Jude Childrens Research Hospital, Memphis, Te
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Contact: Karen Honey
215-573-1850
Journal of Clinical Investigation
22-Mar-2007


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