glutaminase and Precursor-T-Cell-Lymphoblastic-Leukemia-Lymphoma

Acute lymphoblastic leukemia (ALL) is the most common type of pediatric cancer, although about 4 of every 10 cases occur in adults. The enzyme drug l-asparaginase serves as a cornerstone of ALL therapy and exploits the asparagine dependency of ALL cells. In addition to hydrolyzing the amino acid l-asparagine, all FDA-approved l-asparaginases also have significant l-glutaminase coactivity. Since several reports suggest that l-glutamine depletion correlates with many of the side effects of these drugs, enzyme variants with reduced l-glutaminase coactivity might be clinically beneficial if their antileukemic activity would be preserved. Here we show that novel low l-glutaminase variants developed on the backbone of the FDA-approved

Topics: Animals; Antineoplastic Agents; Asparaginase; Cell Line, Tumor; Female; Glutaminase; Glutamine; Humans; Male; Mice, Inbred C57BL; Mice, SCID; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Recombinant Proteins; Toxicity Tests, Acute; Xenograft Model Antitumor Assays