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Leukemic Cells Find Safe Haven in Bone Marrow

St. 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
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