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L-Asparaginase Therapy for Leukemia and Other Malignant Neoplasms: Title and subTitle BreakRemission in Human Leukemia FREE

Joseph M. Hill, MD; Joseph Roberts, PhD; Ellen Loeb, MD; Amanullah Khan, MD; Ayten MacLellan, MD; Robert W. Hill, MD
[+] Author Affiliations

Read before the Acute Leukemia Task Force of the National Institutes of Health, Washington, DC, May 15, 1967.

Reprint requests to 3600 Gaston Ave, Dallas 75246 (Dr. Hill).


JAMA. 1967;202(9):882-888. doi:10.1001/jama.1967.03130220070012
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Enzyme therapy directed at depletion of an amino acid, asparagine, indispensable for tumor cell growth but not required by normal tissues, offers a new and promising approach to the problem of treatment of leukemia and disseminated cancer. Therapy with the enzyme L-asparaginase in three cases of acute lymphatic leukemia resulted in measurable improvement in two advanced cases. In the third case, there was a striking response to large dosage, with rapid necrosis of lymph node masses and clearing of leukemic infiltrates. A laboratory test to detect dependency of tumor cells on asparagine seems helpful for selection of cases for investigation of therapy. Furthermore, a variety of human malignant diseases including acute lymphatic leukemia and acute and chronic granulocytic leukemia have been shown to be asparagine-dependent by this test. Exploitation of further possible nutritional differences offers a fertile field for investigation.

REFERENCES

Kidd, J.G.:  Regression of Transplanted Lymphomas Induced In Vivo by Means of Normal Guinea Pig Serum: I. Course of Transplanted Cancers of Various Kinds in Mice and Rats Given Guinea Pig Serum, Horse Serum, or Rabbit Serum , J Exp Med 98:565-582 ( (Dec) ) 1953;.
Boyse, E.A.; Old, L.J.; and Stockert, E.:  Inhibitory Effect of Guinea Pig Serum on a Number of New Leukemias in Mice , Nature 198:800 ( (May 25) ) 1963;.
Broome, J.D.:  Evidence That the L-Asparaginase Activity of Guinea Pig Serum is Responsible for Its Antilymphoma Effects , Nature 191:1114-1115 ( (Sept 9) ) 1961;.
Clementi, A.:  Desamidation Enzymatique de l'Asparagine , Arch Int Physiol 19:369-398 (No. (4) ) 1922;.
Yellin, T.O., and Wriston, J.C., Jr.:  Antagonism of Purified Asparaginase From Guinea Pig Serum Toward Lymphoma , Science 151:998-999 ( (Feb 25) ) 1966;.
Mashburn, L.T., and Wriston, J.C., Jr.:  Tumor Inhibitory Effect of L-Asparaginase From Escherichia coli , Arch Biochem 105:451-452 ( (May) ) 1964;.
Roberts, J.; Prager, M.D.; and Bachynsky, N.:  The Antitumor Activity of Escherichia coli L-Asparaginase , Cancer Res 26:2213-2217 ( (Oct) ) 1966;.
Hill, J.M.:  Avances en el Tratamiento de las Neoplasias de Tejido Linfoiedo , read before the 17th National Assembly of Surgeons, Mexico City, DF (Nov 14) 1966 .
Old, L.J., et al:  Treatment of Lymphosarcoma in the Dog With L-Asparaginase , Lancet 1:447-448 ( (Feb) ) 1967;.
Dolowy, W.C., et al:  Toxic and Antineoplastic Effects of L-Asparaginase , Cancer 19:1813-1819 ( (Dec) ) 1966;.
Dolowy, W.C., et al:  Response of Intracerebral Gardner Lymphoma to Guinea Pig L-Asparaginase and Escherichia coli L-Asparaginase , Proc Soc Exp Biol Med 123:133-137 ( (Oct) ) 1966;.
Ramadan, M.A., and Greenberg, D.M.:  An Enzymic Micromethod for Determination of Glutamine and Asparagine in Blood , Anal Biochem 6:144-152 ( (Aug) ) 1963;.
Sobin, L.H., and Kidd, J.G.:  A Metabolic Difference Between Two Lines of Lymphoma 6C3HED Cells in Relation to Asparagine , Proc Soc Exp Biol Med 119:325-327 ( (June) ) 1965;.
Hill, J.M.; Loeb, E.; and Oktay, H.I.: " Aggressive Therapy in Leukemia ," in Proceedings of the Eighth International Congress of Hematology , New York: Grune & Stratton, Inc., 1960;, pp 360-367.
Prager, M.D.; Roberts, J.; and Bachynsky, N.:  Immunity to the 6C3HED Ascites Tumor Following Treatment of Tumor-Bearing Mice With E coli L-Asparaginase , J Immunol 98:1045-1052 ( (May) ) 1967;.

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Kidd, J.G.:  Regression of Transplanted Lymphomas Induced In Vivo by Means of Normal Guinea Pig Serum: I. Course of Transplanted Cancers of Various Kinds in Mice and Rats Given Guinea Pig Serum, Horse Serum, or Rabbit Serum , J Exp Med 98:565-582 ( (Dec) ) 1953;.
Boyse, E.A.; Old, L.J.; and Stockert, E.:  Inhibitory Effect of Guinea Pig Serum on a Number of New Leukemias in Mice , Nature 198:800 ( (May 25) ) 1963;.
Broome, J.D.:  Evidence That the L-Asparaginase Activity of Guinea Pig Serum is Responsible for Its Antilymphoma Effects , Nature 191:1114-1115 ( (Sept 9) ) 1961;.
Clementi, A.:  Desamidation Enzymatique de l'Asparagine , Arch Int Physiol 19:369-398 (No. (4) ) 1922;.
Yellin, T.O., and Wriston, J.C., Jr.:  Antagonism of Purified Asparaginase From Guinea Pig Serum Toward Lymphoma , Science 151:998-999 ( (Feb 25) ) 1966;.
Mashburn, L.T., and Wriston, J.C., Jr.:  Tumor Inhibitory Effect of L-Asparaginase From Escherichia coli , Arch Biochem 105:451-452 ( (May) ) 1964;.
Roberts, J.; Prager, M.D.; and Bachynsky, N.:  The Antitumor Activity of Escherichia coli L-Asparaginase , Cancer Res 26:2213-2217 ( (Oct) ) 1966;.
Hill, J.M.:  Avances en el Tratamiento de las Neoplasias de Tejido Linfoiedo , read before the 17th National Assembly of Surgeons, Mexico City, DF (Nov 14) 1966 .
Old, L.J., et al:  Treatment of Lymphosarcoma in the Dog With L-Asparaginase , Lancet 1:447-448 ( (Feb) ) 1967;.
Dolowy, W.C., et al:  Toxic and Antineoplastic Effects of L-Asparaginase , Cancer 19:1813-1819 ( (Dec) ) 1966;.
Dolowy, W.C., et al:  Response of Intracerebral Gardner Lymphoma to Guinea Pig L-Asparaginase and Escherichia coli L-Asparaginase , Proc Soc Exp Biol Med 123:133-137 ( (Oct) ) 1966;.
Ramadan, M.A., and Greenberg, D.M.:  An Enzymic Micromethod for Determination of Glutamine and Asparagine in Blood , Anal Biochem 6:144-152 ( (Aug) ) 1963;.
Sobin, L.H., and Kidd, J.G.:  A Metabolic Difference Between Two Lines of Lymphoma 6C3HED Cells in Relation to Asparagine , Proc Soc Exp Biol Med 119:325-327 ( (June) ) 1965;.
Hill, J.M.; Loeb, E.; and Oktay, H.I.: " Aggressive Therapy in Leukemia ," in Proceedings of the Eighth International Congress of Hematology , New York: Grune & Stratton, Inc., 1960;, pp 360-367.
Prager, M.D.; Roberts, J.; and Bachynsky, N.:  Immunity to the 6C3HED Ascites Tumor Following Treatment of Tumor-Bearing Mice With E coli L-Asparaginase , J Immunol 98:1045-1052 ( (May) ) 1967;.
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