@article{bb85595a3326484c808f93044053e6a7,
title = "Glutaminase activity of L-asparaginase contributes to durable preclinical activity against acute lymphoblastic leukemia",
abstract = "We and others have reported that the anticancer activity of L-asparaginase (ASNase) against asparagine synthetase (ASNS)-positive cell types requires ASNase glutaminase activity, whereas anticancer activity against ASNS-negative cell types does not. Here, we attempted to disentangle the relationship between asparagine metabolism, glutamine metabolism, and downstream pathways that modulate cell viability by testing the hypothesis that ASNase anticancer activity is based on asparagine depletion rather than glutamine depletion per se. We tested ASNase wild-type (ASNaseWT) and its glutaminase-deficient Q59L mutant (ASNaseQ59L) and found that ASNase glutaminase activity contributed to durable anticancer activity against xenografts of the ASNS-negative Sup-B15 leukemia cell line in NOD/SCID gamma mice, whereas asparaginase activity alone yielded a mere growth delay. Our findings suggest that ASNase glutaminase activity is necessary for durable, single-agent anticancer activity in vivo, even against ASNS-negative cancer types.",
author = "Chan, {Wai Kin} and Horvath, {Thomas D.} and Lin Tan and Todd Link and Harutyunyan, {Karine G.} and Pontikos, {Michael A.} and Andriy Anishkin and Di Du and Martin, {Leona A.} and Eric Yin and Rempe, {Susan B.} and Sergei Sukharev and Marina Konopleva and Weinstein, {John N.} and Lorenzi, {Philip L.}",
note = "Funding Information: Institute of Texas grant number RP130397 (J.N. Weinstein and P.L. Lorenzi); NIH high-end instrument grant 1S10OD012304-01 (P.L. Lorenzi), the Chapman Foundation, and the Michael and Susan Dell Foundation (honoring Lorraine Dell). SNL is a multimission laboratory managed and operated by NTESS for the US DOE, NNSA, under contract DE-NA-0003525 (S.B. Rempe). Sup-B15-luc cells were a kind gift from Michael Jensen (Seattle Children's Research Hospital). Funding Information: This work was supported in part by NCI grant numbers CA143883 (J.N. Weinstein), CA083639 (J.N. Weinstein), CA235510 (J.N. Weinstein), and CA016672 (J.N. Weinstein and P.L. Lorenzi); Cancer Prevention and Research Institute of Texas grant number RP130397 (J.N. Weinstein and P.L. Lorenzi); NIH high-end instrument grant 1S10OD012304-01 (P.L. Lorenzi), the Chapman Foundation, and the Michael and Susan Dell Foundation (honoring Lorraine Dell). SNL is a multimission laboratory managed and operated by NTESS for the US DOE, NNSA, under contract DE-NA-0003525 (S.B. Rempe). Sup-B15-luc cells were a kind gift from Michael Jensen (Seattle Children's Research Hospital). Funding Information: This work was supported in part by NCI grant numbers CA143883 (J.N. Weinstein), CA083639 (J.N. Weinstein), CA235510 (J.N. Weinstein), and CA016672 (J.N. Weinstein and P.L. Lorenzi); Cancer Prevention and Research Publisher Copyright: {\textcopyright} 2019 American Association for Cancer Research.",
year = "2019",
doi = "10.1158/1535-7163.MCT-18-1329",
language = "English (US)",
volume = "18",
pages = "1587--1592",
journal = "Molecular cancer therapeutics",
issn = "1535-7163",
publisher = "American Association for Cancer Research Inc.",
number = "9",
}