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Background Mesenchymal cells (MSCs) in bone marrow (BM) may produce asparagine and form protective niches for leukemic cells. In vitro, this led to high levels of asparagine and conferred asparaginase resistance to acute lymphoblastic leukemia (ALL) cells. The aim of this study was to investigate whether MSCs or other cells in BM indeed produce such significant amounts of asparagine in vivo as to result in clinical asparaginase resistance. Procedure Twenty-six patients with newly diagnosed ALL were enrolled. All children received induction chemotherapy according to the Dutch Childhood Oncology Group (DCOG) ALL-10 protocol. Asparaginase was administered from days 12–33. Asparaginase, asparagine, aspartic acid, glutamine, and glutamic acid levels were measured in BM and blood at diagnosis, days 15, 33, and 79. Results Median asparaginase trough levels were not significantly different at days 15 and 33. Only at diagnosis, asparagine level was significantly higher in BM than in blood (P = 0.001). Asparagine levels were all below the lower limit of quantification in BM and blood at days 15 and 33. However, aspartic acid level in BM was significantly higher than in blood (P

_To the Editor:_ Asparaginase is an enzyme which hydrolyses asparagine into aspartic acid and ammonia. Levels of asparaginase activity are relatively easy to measure, and a trough level >100 U/L is associated with complete asparagine depletion. So, the measurement of levels of asparaginase activity is a very useful tool to monitor asparaginase activities in clinical practice. However, these assays are not available in all countries in contrast to ammonia measurements. Recently, a Polish study group published ammonia levels of 87 children during acute lymphoblastic leukemia (ALL) induction therapy. They concluded that the ammonia concentration reflects the levels of asparaginase activity and could be useful when asparaginase activity assays are not available. We evaluated if ammonia levels could be used as a surrogate marker of levels of asparaginase activity. [...]