{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T10:40:05Z","timestamp":1776940805434,"version":"3.51.4"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Acute myeloid leukemia (AML) remains a malignancy with poor prognosis andfrequent resistance to standard therapies, underscoring the urgent need for novel treatmentstrategies. In this preclinical study, we evaluated the anti-leukemic efficacy of EBD-300, a novelmammalian-derived asparaginase lacking glutaminase activity, in combination with Venetoclax(VEN).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>EBD-300 monotherapy exhibited significant activity in AML cell lines harboringchromosome 7\/7q deletions, which are likely dependent on extracellular asparagine due to thepresence of only a single copy of the asparagine synthetase (ASNS) gene - the enzymeresponsible for endogenous asparagine synthesis. The combination of EBD-300 with VENdecreased the IC50 values of some VEN-resistant AML cell lines and reduced the colony-formingcapacity of primary AML patient samples. In patient-derived xenograft (PDX) mouse models,EBD-300, alone or in combination with VEN, significantly reduced leukemic burden in theperipheral blood, bone marrow, and spleen, and improved overall survival in one model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Although survival benefits were observed in some, but not all, models, suggestingpotential model-specific effects, these findings collectively support a potential therapeutic roleEBD-300 in combination with VEN in AML. While weight loss was observed, EBD-300 mayrepresent a potentially safer alternative to conventional bacterial asparaginases by mitigatingthe adverse effects typically associated with the glutaminase coactivity of the bacterialasparaginases, an observation that requires further investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2025.1606239","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T13:08:31Z","timestamp":1770728911000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A mammalian, glutaminase-free asparaginase enhances venetoclax activity in preclinical AML models with chromosome 7 deletion"],"prefix":"10.3389","volume":"15","author":[{"given":"Dhabya","family":"Majid","sequence":"first","affiliation":[{"name":"Department of Leukemia, The University of Texas MD Anderson Cancer Center","place":["Houston, TX, United 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Zhang","family":"Tatarata","sequence":"additional","affiliation":[{"name":"Department of Leukemia, The University of Texas MD Anderson Cancer Center","place":["Houston, TX, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica L.","family":"Root","sequence":"additional","affiliation":[{"name":"Department of Leukemia, The University of Texas MD Anderson Cancer Center","place":["Houston, TX, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Araceli Isabella","family":"Garza","sequence":"additional","affiliation":[{"name":"Department of Leukemia, The University of Texas MD Anderson Cancer Center","place":["Houston, TX, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mhd Yousuf","family":"Yassouf","sequence":"additional","affiliation":[{"name":"Department of Leukemia, The University of Texas MD Anderson Cancer Center","place":["Houston, TX, United 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