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Leukemic cells find safe haven in bone marrow

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, the researchers reported. Mesenchymal cells give rise to a variety of different tissues, such as osteoblasts (bone-building cells) and chondrocytes (cartilage-building cells), and form the nurturing environment where normal blood cells and leukemic cells grow.

"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 St. Jude Oncology and Pathology departments.

Campana is senior author of the report that appears in the online pre-publication issue of "The Journal of Clinical Investigation."

"Our findings indicate that the level of activity of the "ASNS" gene in the mesenchymal cells is key to protecting leukemic cells in the bone marrow from asparaginase," Campana said. "This insight will help researchers 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 "The Journal of Clinical Investigation" paper. The "ASNS" gene controls production of the enzyme asparagine synthetase (ASNS), which leukemic cells use to make asparagine.

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Source:St. Jude Children's Research Hospital


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