title: Discovery of why acute lymphoblastic leukaemia cells are killed by asparaginase: Adventures of a young post-doctoral student, Bertha K Madras.
abstract: A surprising finding was made by JG Kidd (1909-1991) that guinea pig serum could make tumours disappear in mice. A later finding made by JD Broome (1939-) showed that asparaginase could suppress or kill tumour cells. However, the major mystery was why were only tumour cells but not normal cells affected by the asparaginase? The biology underlying this mechanism was unravelled by a young post-doctoral student, Bertha K Madras (1942-) who hypothesized that cells with low asparagine synthetase are those that die following treatment with asparaginase. To test her theory, Madras developed an assay for asparagine synthetase. The hypothesis was supported by the results that cells with normal asparagine synthetase were protected, while cells with low levels of this enzyme were killed by asparaginase. The findings provide a clinical guide for the use of asparaginase in acute lymphoblastic leukaemia in children and adults.
authors.affiliation: Department of Pharmacology, University of Toronto, Ontario, Canada Philip.Seeman@utoronto.ca.
authors.forename: Philip
authors.initials: P
authors.lastname: Seeman
mesh_terms: D000818:Animals; D001215:Asparaginase / Q000266:history* / Q000494:pharmacology / Q000627:therapeutic use; D001217:Aspartate-Ammonia Ligase / Q000172:deficiency; D035843:Biomedical Research / Q000266:history*; D002170:Canada; D049673:History, 20th Century; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000266:history; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000201:enzymology / Q000266:history*; D051381:Rats; D014481:United States
chemical_list: D001215:Asparaginase; D001217:Aspartate-Ammonia Ligase
keywords: Asparaginase; cancer; lymphocytes; white blood cells