γ-glutamyl hydrolase and folylpolyglutamate synthetase activities predict polyglutamylation of methotrexate in acute leukemias Journal Article
| Authors: | Longo, G. S. A.; Gorlick, R.; Tong, W. P.; Lin, S.; Steinherz, P.; Bertino, J. R. |
| Article Title: | γ-glutamyl hydrolase and folylpolyglutamate synthetase activities predict polyglutamylation of methotrexate in acute leukemias |
| Abstract: | Decreased methotrexate (MTX) long-chain polyglutamate formation is associated with MTX resistance whereas high levels of MTX polyglutamate accumulation are found in the blasts of leukemia patients who respond to therapy and have improved outcome. The steady-state level of long-chain MTX polyglutamates depends on the balance of activities of two enzymes: folylpolyglutamate synthetase (FPGS), which adds glutamates to MTX in a y-carboxyl linkage, and -y-glutamyl hydrolase (GGH) or conjugase, which sequentially removes the terminal glutamate residue of MTX polyglutamates. FPGS and GGH activities as well as the formation of total and long-chain MTX polyglutamates were measured after incubation with [3H]MTX in 15 blast samples from patients with acute leukemias (myeloid and lymphoid). The ratio between GGH and FPGS activities was better at predicting the amount of polyglutamate accumulated in the 24-h [3H]MTX assay compared to the determination of either activity alone. The linear regression curve relating the relative levels of long-chain polyglutamates/total polyglutamates with the ratio of GGH/FPGS showed an r value of 0.81 (P < 0.001). These data suggest that the evaluation of both these enzymes at diagnosis may be used as a predictor of MTX polyglutamylation and therefore for response to MTX therapy and outcome. Copyright © 1997 Cognizant Comm. Corp. |
| Keywords: | child; preschool child; child, preschool; methotrexate; biological marker; biological markers; metabolism; antimetabolites, antineoplastic; enzymology; leukemia, myeloid; drug derivative; acute lymphocytic leukemia; lymphatic leukemia; antineoplastic antimetabolite; acute disease; myeloid leukemia; gamma-glutamyl hydrolase; gamma glutamyl hydrolase; polyglutamic acid; peptide synthase; peptide synthases; leukemia, lymphocytic; humans; human; article; acute myelocytic leukemia; methotrexate polyglutamates; folylpolyglutamate synthase; methotrexate polyglutamate; γ-giutamyl hydrolase; folypolyglutamate synthetase |
| Journal Title: | Oncology Research |
| Volume: | 9 |
| Issue: | 5 |
| ISSN: | 0965-0407 |
| Publisher: | Cognizant Communication Corporation |
| Date Published: | 1997-01-01 |
| Start Page: | 259 |
| End Page: | 263 |
| Language: | English |
| PUBMED: | 9306433 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 17 March 2017 -- Source: Scopus |
