biostudies-literatureNguyen HAU.S. Department of Veterans Affairs (VA)BLRD VANIBIB NIH HHSFonds Wetenschappelijk Onderzoek (FWO)Vlaamse Liga Tegen Kanker (VLK)European Hematology AssociationStichting Tegen Kanker (Fondation Contre le Cancer)HHS | NIH | National Institute of Biomedical Imaging and Bioengineering (NIBIB)1549-1560https://www.ebi.ac.uk/biostudies/studies/S-EPMC5856643biostudies-literatureUnknown78(6)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 <i>Erwinia chrysanthemi</i> l-asparaginase were highly efficaCancer researchA Novel l-Asparaginase with low l-Glutaminase Coactivity Is Highly Efficacious against Both T- and B-cell Acute Lymphoblastic Leukemias &lt;i&gt;In Vivo&lt;/i&gt;.PMC5856643I01 BX001919365Y9115W365W3415WFWO17/PDO/111TRTH104I01BX0019193G0C4713RO1 EB013685R01 EB013685Bosland MCPeirs SLiu LLammens TMerrill BJDe Moerloose BSchlicht MJLyubimov AVSaunthararajah YKabirov KKCaffrey MMahmud DLGoossens SSchalk AMLavie AAntanasijevic AVan Vlierberghe PZhang JYNguyen HARondelli DKajdacsy-Balla ASu YMondelaers VOh AfalseA Novel l-Asparaginase with low l-Glutaminase Coactivity Is Highly Efficacious against Both T- and B-cell Acute Lymphoblastic Leukemias &lt;i&gt;In Vivo&lt;/i&gt;.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 <i>Erwinia chrysanthemi</i> l-asparaginase were highly effica2018-01-01T00:00:00Z2018 Mar2026-06-04T06:45:09.615Z2019-08-04T07:03:08ZS-EPMC58566432934352310.1158/0008-5472.CAN-17-210610.1158/0008-5472.can-17-2106