Skip to main content
NCBI home page
British Medical Journal logoLink to British Medical Journal
. 1976 May 29;1(6021):1317–1319. doi: 10.1136/bmj.1.6021.1317

Bacterial glutaminase in treatment of acute leukaemia.

A S Spiers, H E Wade
PMCID: PMC1640338  PMID: 773514

Abstract

A glutaminase-asparaginase enzyme from Achromobacter sp has antitumour activity in vitro and in animals. Glutaminase was administered in doses of 3500-20 000 IU/m2 body surface area/day to six patients with acute lymphoblastic leukaemia (ALL) and three patients with acute myeloid leukaemia (AML). The enzyme had a blood half life of 80 minutes but depletion of blood glutamine persisted for 12 hours after single doses. Seven patients, including four (two with AML and two with ALL) resistant to asparaginase, received repeated doses of glutaminase. Antileukaemic effects were observed in all seven; one elderly patient developed metabolic acidosis. Study of this new antileukaemic agent in patients with acute leukaemia at an earlier stage of their disease is now justified.

Full text

PDF
1317

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Borella L., Journey L. J., Hiramoto R. In vivo and in vitro effects of the L-asparaginase fraction of guinea pig serum on the 6C3HED ascites lymphosarcoma. Cancer Res. 1966 Dec;26(12):2451–2460. [PubMed] [Google Scholar]
  2. Boyse E. A., Old L. J., Campbell H. A., Mashburn L. T. Suppression of murine leukemias by L-asparaginase. Incidence of sensitivity among leukemias of various types: comparative inhibitory activities of guinea pig serum L-asparaginase and Escherichia coli L-asparaginase. J Exp Med. 1967 Jan 1;125(1):17–31. doi: 10.1084/jem.125.1.17. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Capizzi R. L., Bertino J. R., Handschumacher R. E. L-asparaginase. Annu Rev Med. 1970;21:433–444. doi: 10.1146/annurev.me.21.020170.002245. [DOI] [PubMed] [Google Scholar]
  4. Catovsky D., Galetto J., Okos A., Galton D. A., Wiltshaw E., Stathopoulos G. Prolymphocytic leukaemia of B and T cell type. Lancet. 1973 Aug 4;2(7823):232–234. doi: 10.1016/s0140-6736(73)93135-8. [DOI] [PubMed] [Google Scholar]
  5. Hill J. M., Loeb E., MacLellan A., Khan A., Roberts J., Shields W. F., Hill N. O. Response to highly purified L-asparaginase during therapy of acute leukemia. Cancer Res. 1969 Aug;29(8):1574–1580. [PubMed] [Google Scholar]
  6. Holcenberg J. S., Schmer G., Teller D. C. Biologic and physical properties of succinylated and glycosylated Acinetobacter glutaminase-asparaginase. J Biol Chem. 1975 Jun 10;250(11):4165–4170. [PubMed] [Google Scholar]
  7. Holcenberg J. S., Tang E., Dolowy W. C. Effect of Acinetobacter glutaminase-asparaginase treatment on free amino acids in mouse tissues. Cancer Res. 1975 May;35(5):1320–1325. [PubMed] [Google Scholar]
  8. King O. Y., Wilbur J. R., Mumford D. M., Sutow W. W. Therapy with Erwinia L-asparaginase in children with acute leukemia after anaphylaxis to E. coli L-asparaginase. Cancer. 1974 Mar;33(3):611–614. doi: 10.1002/1097-0142(197403)33:3<611::aid-cncr2820330303>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
  9. Roberts J., Holcenberg J. S., Dolowy W. C. Isolation, crystallization, and properties of Achromobacteraceae glutaminase-asparaginase with antitumor activity. J Biol Chem. 1972 Jan 10;247(1):84–90. [PubMed] [Google Scholar]
  10. Schmid F. A., Roberts J. Antineoplastic and toxic effects of Acinetobacter and Pseudomonas glutaminase-asparaginases. Cancer Chemother Rep. 1974 Nov-Dec;58(6):829–840. [PubMed] [Google Scholar]
  11. Schrek R., Batra K. V., Holcenberg J. S., Roberts J., Dolowy W. C. Effect of L-glutaminase on transformation and DNA synthesis of normal lymphocytes. Acta Haematol. 1972;48(1):12–15. doi: 10.1159/000208432. [DOI] [PubMed] [Google Scholar]
  12. Schrek R., Holcenberg J. S., Batra K. V., Roberts J., Dolowy W. C. Effect of asparagine and glutamine deficiency on normal and leukemic cells. J Natl Cancer Inst. 1973 Oct;51(4):1103–1107. doi: 10.1093/jnci/51.4.1103. [DOI] [PubMed] [Google Scholar]
  13. Schrek R., Holcenberg J. S., Roberts J., Dolowy W. C. In vitro cytocidal effect of L-glutaminase on leukaemic lymphocytes. Nature. 1971 Jul 23;232(5308):265–265. doi: 10.1038/232265a0. [DOI] [PubMed] [Google Scholar]
  14. Tallal L., Tan C., Oettgen H., Wollner N., McCarthy M., Helson L., Burchenal J., Karnofsky D., Murphy M. L. E. coli L-asparaginase in the treatment of leukemia and solid tumors in 131 children. Cancer. 1970 Feb;25(2):306–320. doi: 10.1002/1097-0142(197002)25:2<306::aid-cncr2820250206>3.0.co;2-h. [DOI] [PubMed] [Google Scholar]
  15. Wade H. E., Phillips B. P. Automated determination of bacterial asparaginase and glutaminase. Anal Biochem. 1971 Nov;44(1):189–199. doi: 10.1016/0003-2697(71)90360-5. [DOI] [PubMed] [Google Scholar]

Articles from British Medical Journal are provided here courtesy of BMJ Publishing Group

RESOURCES