Leukemic Cells Find Safe Haven in Bone MarrowSt. Jude study shows mesenchymal cells in bone marrow supply leukemic cells with the amino acid asparagine, restoring this critical nutrient when it is depleted by the cancer drug asparaginase
MEMPHIS, Tenn., March 22, 2007 /PRNewswire/ -- The cancer drug asparaginase fails to help cure some children with acute lymphoblastic leukemia (ALL) because molecules released by certain cells in the bone marrow counteract the effect of that drug, according to investigators at St. Jude Children's Research Hospital.
The researchers showed that mesenchymal cells in the bone marrow create a protective niche for leukemic cells by releasing large amounts of asparagine, an amino acid that nearby leukemic cells must have to survive but do not make efficiently. This extra supply of asparagine helps leukemic cells survive treatment with asparaginase, a drug that normally would deplete their supply of this vital nutrient.
"Leukemic cells that resist asparaginase and survive in this protective niche of the bone marrow might be the reason that leukemia recurs in some children who have been treated with this drug," said Dario Campana, M.D., Ph.D., a member of the Oncology and Pathology departments at St. Jude. Campana is senior author of a report that appears in the online pre-publication issue of "The Journal of Clinical Investigation."
"This insight from this study will help researchers to find ways to disrupt this safe haven for leukemic cells that need asparagine," added James R. Downing, M.D., St. Jude scientific director and chair of the Pathology department. Downing is a co-author of paper.
The study's findings also suggest that drugs now being developed to block the enzyme that makes asparagine 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 rate of recurrence of ALL and continue our successful efforts to increase the survival rate of ALL."
The experiments for this study were performed primarily by Shotaro Iwamoto, M.D., first author of the paper, and Keichiro Mihara, a co-author, postdoctoral fellows in Campana's laboratory.
This work was supported in part by the National Cancer Institute and ALSAC.
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fundraising organization. For more information, please visit www.stjude.org.
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Posted: March 2007