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Leukemic cells find safe haven in bone marrow

p>The study’s findings also suggest that drugs now being developed to block ASNS should be tested to see if they also prevent mesenchymal cells from making this amino acid. In addition, the ability of mesenchymal cells to make asparagine might be decreased by cancer drugs that are already known to disrupt the activity of those cells.

"Because asparaginase is so widely used to treat ALL, this new insight into how mesenchymal cells protect leukemic cells is very important," said Ching-Hon Pui, M.D., chair of the Oncology department and American Cancer Society Professor at St. Jude. "The more we learn about the molecular interactions between these cells, the more likely we’ll be able to enhance the anti-leukemic action of asparaginase and perhaps other anti-leukemic drugs as well," said Pui, a co-author of the paper. "That would reduce the recurrence rate of ALL and continue our successful efforts to increase the survival rate of ALL."

Previous research at St. Jude and elsewhere had shown that direct contact with bone marrow mesenchymal cells is essential for the long-term survival and multiplication of leukemic lymphoblasts. In the current study, the team found that the gene for ASNS was more than 20 times active in producing this enzyme in mesenchymal cells than in ALL cells.

Experiments performed by co-authors Shotaro Iwamoto, M.D., and Keichiro Mihara, postdoctoral fellows in Campana’s laboratory, demonstrated that ALL cells from different patients became much more resistant to asparaginase when cultured on top of a layer of mesenchymal cells. In order to determine whether it was the high levels of asparagine released by mesenchymal cells that protected ALL cells from asparaginase, the St. Jude team repeated the experiment, but blocked the ability of mesenchymal cells to make the ASNS enzyme and produce asparagine. In this case, the protective effect of mesenchymal cells was eliminated. Conversely, when the researchers caused the AS
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Source:St. Jude Children's Research Hospital


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