Ex vivo activity of methotrexate versus novel antifolate inhibitors of dihydrofolate reductase and thymidylate synthase against childhood leukemia cells

Clinical Cancer Research

Volumn 4, Issue 10, 1998, Pages 2399-2410

  Mauritz, Robert ^a   Bekkenk, Marcel W ^a   Rots, Marianne G ^a   Pieters, Rob ^a   Mini, Enrico ^b   Van Zantwijk, Christina H ^a   Veerman, Anjo J P ^a   Peters, Godefridus J ^a   Jansen, Gerrit ^a  

^a VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^b UNIVERSITY OF FLORENCE   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

2 [5 [[(1,2 DIHYDRO 3 METHYL 1 OXOBENZO[F]QUINAZOLIN 9 YL)METHYL]AMINO] 1 OXO 2 ISOINDOLINYL]GLUTARIC ACID; ANTILEUKEMIC AGENT; ANTINEOPLASTIC AGENT; DIHYDROFOLATE REDUCTASE INHIBITOR; EDATREXATE; FOLIC ACID ANTAGONIST; METHOTREXATE; NOLATREXED; RALTITREXED; THYMIDYLATE SYNTHASE INHIBITOR; TRIMETREXATE; UNCLASSIFIED DRUG;

ACUTE LYMPHOBLASTIC LEUKEMIA; ACUTE NONLYMPHOCYTIC LEUKEMIA; ADOLESCENT; ARTICLE; CANCER CHEMOTHERAPY; CANCER INHIBITION; CHILD; CHILDHOOD LEUKEMIA; CLINICAL ARTICLE; CONTROLLED STUDY; DRUG EFFICACY; FEMALE; HUMAN; HUMAN CELL; INFANT; LEUKEMIA CELL; LONG TERM EXPOSURE; MALE; PRIORITY JOURNAL; TREATMENT OUTCOME;

ANTIMETABOLITES, ANTINEOPLASTIC; CHILD; DRUG RESISTANCE, NEOPLASM; FOLIC ACID ANTAGONISTS; HUMANS; LEUKEMIA, LYMPHOCYTIC, ACUTE, L1; LEUKEMIA, NONLYMPHOCYTIC, ACUTE; METHOTREXATE; THYMIDYLATE SYNTHASE; TUMOR CELLS, CULTURED;

EID: 0031752949     PISSN: 10780432     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (59)

1. Bertino, J. R. Karnofsky Memorial Lecture. Ode to methotrexate. J. Clin. Oncol., 11: 5-14, 1993.
2. Pieters, R., Klumper, E., Kaspers, G. J., and Veerman, A. J. Everything you always wanted to know about cellular drug resistance in childhood acute lymphoblastic leukemia. Crit. Rev. Oncol.-Hematol., 25: 11-26, 1997.
3. Pui, C. H. Childhood leukemias. N. Engl. J. Med., 332: 1618-1630, 1995.
4. Lin, J. T., Tong, W. P., Trippett, T. M., Niedzwiecki, D., Tao, Y., Tan, C., Steinherz, P., Schweitzer, B. I., and Bertino, J. R. Basis for natural resistance to methotrexate in human acute non-lymphocytic leukemia. Leuk. Res., 15: 1191-1196, 1991.
5. Rots, M. G., Pieters, R., Noordhuis, P., Van Zantwijk, C. H., Peters, G. J., Veerman, A. J. P., and Jansen, G. Role of folylpolyglutamate synthetase (FPGS) and folylpolyglutamate hydrolase (FPGH) in methotrexate (MTX) polyglutamylation in childhood leukemia. Proc. Am. Assoc. Cancer Res., 38: 162, 1997.
6. Pieters, R., Huismans, D. R., Loonen, A. H., Hahlen, K., Van Der Does-Van Den Berg, A., Van Wering, E. R., and Veerman, A. J. P. Relation of cellular drug resistance to long-term clinical outcome in childhood acute lymphoblastic leukaemia. Lancet, 338: 399-403, 1991.
7. Kaspers, G. J., Veerman, A. J., Pieters, R., Van Zantwijk, C. H., Smets, L. A., Van Wering, E. R., and Van Der Does-Van Den Berg, A. In vitro cellular drug resistance and prognosis in newly diagnosed childhood acute lymphoblastic leukemia. Blood, 90: 2723-2729, 1997.
8. Hughes, J. M., deFazio, A., and Tattersall, M. H. Modulation of antifolate cytotoxicity by metabolites from dying cells in a lymphocyte clonal assay. Br. J. Cancer, 57: 459-463, 1988.
9. Haber, M., Madafiglio, J., and Morris, M. D. Methotrexate cytotoxicity determination using the MTT assay following enzymatic depletion of thymidine and hypoxanthine. J. Cancer Res. Clin. Oncol., 119: 315-317, 1993.
10. Pinedo, H. M., Zaharko, D. S., Bull, J. M., and Chabner, B. A. The reversal of methotrexate cytotoxicity to mouse bone marrow cells by leucovorin and nucleosides. Cancer Res., 36: 4418-4424, 1976.
11. Gorlick, R., Goker, E., Trippett, T., Waltham, M., Banerjee, D., and Bertino, J. R. Intrinsic and acquired resistance to methotrexate in acute leukemia. N. Engl. J. Med., 335: 1041-1048, 1996.
12. Peters, G. J., and Jansen, G. Resistance to antimetabolites. In: R. L. Schilsky, G. A. Milano, and M. J. Ratain (eds.). Principles of Antineoplastic Drug Development and Pharmacology, pp. 543-585. New York, Basel, Hong Kong: Marcel Dekker, Inc., 1996.
13. Sirotnak, F. M., Moccio, D. M., Kelleher, L. E., and Goutas, L. J. Relative frequency and kinetic properties of transport-defective phenotypes amone methotrexate-resistant L1210 clonal cell lines derived in vivo. Cancer Res., 41: 4447-4452, 1981.
14. Henderson, G. B., Tsuji, J. M., and Kumar, H. P. Characterization of the individual transport routes that mediate the influx and efflux of methotrexate in CCRF-CEM human lymphoblastic cells. Cancer Res., 46: 1633-1638, 1986.
15. Schuetz, J. D., Matherly, L. H., Westin, E. H., and Goldman, I. D. Evidence for a functional defect in the translocation of the methotrexate transport carrier in a methotrexate-resistant murine L1210 leukemia cell line. J. Biol. Chem., 263: 9840-9847, 1988.
16. Cowan, K. H., and Jolivet, J. A methotrexate-resistant human breast cancer cell line with multiple defects, including diminished formation of methotrexate polyglutamates. J. Biol. Chem., 259: 10793-10800, 1984.
17. McCloskey, D. E., McGuire, J. J., Russell, C. A., Rowan, B. G., Bertino, J. R., Pizzorno, G., and Mini, E. Decreased folylpolyglutamate synthetase activity as a mechanism of methotrexate resistance in CCRF-CEM human leukemia sublines. J. Biol. Chem., 266: 6181-6187, 1991.
18. Alt, F. W., Kellems, R. E., Bertino, J. R., and Schimke, R. T. Selective multiplication of dihydrofolate reductase genes in methotrexate-resistant variants of cultured murine cells. J. Biol. Chem., 253: 1357-1370, 1978.
19. Jackson, R. C., and Niethammer, D. Acquired methotrexate resistance in lymphoblasts resulting from altered kinetic properties of dihydrofolate reductase. Eur. J. Cancer, 13: 567-575, 1977.
20. Matherly, L. H., Taub, J. W., Ravindranath, Y., Proefke, S. A., Wong, S. C., Gimotty, P., Buck, S., Wright, J. E., and Rosowsky, A. Elevated dihydrofolate reductase and impaired methotrexate transport as elements in methotrexate resistance in childhood acute lymphoblastic leukemia. Blood, 85: 500-509, 1995.
21. Goker, E., Waltham, M., Kheradpour, A., Trippett, T., Mazumdar, M., Elisseyeff, Y., Schnieders, B., Steinherz, P., Tan, C., and Berman, E. Amplification of the dihydrofolate reductase gene is a mechanism of acquired resistance to methotrexate in patients with acute lymphoblastic leukemia and is correlated with p53 gene mutations. Blood, 86: 677-684, 1995.
22. Whitehead, V. M., Rosenblatt, D. S., Vuchich, M. J., Shuster, J. J., Witte, A., and Beaulieu, D. Accumulation of methotrexate and methotrexate polyglutamates in lymphoblasts at diagnosis of childhood acute lymphoblastic leukemia: a pilot prognostic factor analysis. Blood, 76: 44-49, 1990.
23. Trippett, T., Schlemmer, S., Elisseyeff, Y., Goker, E., Wachter, M., Steinherz, P., Tan, C., Berman, E., Wright, J. E., and Rosowsky, A. Defective transport as a mechanism of acquired resistance to methotrexate in patients with acute lymphocytic leukemia. Blood, 80: 1158-1162, 1992.
24. Gorlick, R., Goker, E., Trippett, T., Steinherz, P., Elisseyeff, Y., Mazumdar, M., Flintoff, W. F., and Bertino, J. R. Defective transport is a common mechanism of acquired methotrexate resistance in acute lymphocytic leukemia and is associated with decreased reduced folate carrier expression. Blood, 89: 1013-1018, 1997.
25. Masson, E., Relling, M. V., Synold, T. W., Liu, Q., Schuetz, J. D., Sandlund, J. T., Pui, C. H., and Evans, W. E. Accumulation of methotrexate polyglutamates in lymphoblasts is a determinant of antileukemic effects in vivo. A rationale for high-dose methotrexate. J. Clin. Investig., 97: 73-80, 1996.
26. Barredo, J., and Moran, R. G. Determinants of antifolate cytotoxicity: folylpolyglutamate synthetase activity during cellular proliferation and development. Mol. Pharmacol., 42: 687-694, 1992.
27. Barredo, J. C., Synold, T. W., Laver, J., Relling, M. V., Pui, C. H., Priest, D. G., and Evans, W. E. Differences in constitutive and post-methotrexate folylpolyglutamate synthetase activity in B-lineage and T-lineage leukemia. Blood, 84: 564-569, 1994.
28. Peters, G. J., and Van der Wilt, C. L. Thymidylate synthase as a target in cancer chemotherapy. Biochem. Soc. Trans., 23: 884-888, 1995.
29. Jackman, A. L., and Judson, I. R. The new generation of thymidylate synthase inhibitors in clinical study. Exp. Opin. Investig. New Drugs, 5: 719-736, 1996.
30. Jackman, A. L., Taylor, G. A., Gibson, W., Kimbell, R., Brown, M., Calvert, A. H., Judson, I. R., and Hughes, L. R. ICI D1694, a quinazoline antifolate thymidylate synthase inhibitor that is a potent inhibitor of L1210 tumor cell growth in vitro and in vivo: a new agent for clinical study. Cancer Res., 51: 5579-5586, 1991.
31. Duch, D. S., Banks, S., Dev, I. K., Dickerson, S. H., Ferone, R., Heath, L. S., Humphreys, J., Knick, V., Pendergast, W., and Singer, S. Biochemical and cellular pharmacology of 1843U89, a novel benzoquinazoline inhibitor of thymidylate synthase. Cancer Res., 53: 810-818, 1993.
32. Webber, S. E., Bleckman, T. M., Attard, J., Deal, J. G., Kathardekar, V., Welsh, K. M., Webber, S., Janson, C. A., Matthews, D. A., and Smith, W. W. Design of thymidylate synthase inhibitors using protein crystal structures: the synthesis and biological evaluation of a novel class of 5-substituted quinazolinones. J. Med. Chem., 36: 733-746, 1993.
33. Schornagel, J. H., Verweij, J., De Mulder, P. H. M., Cognetti, F., Vermerken, J. B., Cappelaere, P., Armand, J. P., Wildiers, J., De Graeff, A., and Clavel, M. Randomized Phase III trial of edatrexate versus methotrexate in patients with metastatic and/or recurrent squamous cell carcinoma of the head and neck: a European Organization for Research and Treatment of Cancer Head and Neck Cancer Cooperative Group study. J. Clin. Oncol., 13: 1649-1655, 1995.
34. Pieters, R., Loonen, A. H., Huismans, D. R., Broekema, G. J., Dirven, M. W., Heyenbrok, M. W., Hahlen, K., and Veerman, A. J. In vitro drug sensitivity of cells from children with leukemia using the MTT assay with improved culture conditions. Blood, 76: 2327-2336, 1990.
35. Rots, M. G., Kaspers, G. J., Noordhuis, P., Van Zantwijk, C. H., Veerman, A. J. P., Peters, G. J., and Pieters, R. In vitro cytotoxicity tests fail to determine resistance to methotrexate of childhood leukemia cells. Leukemia (Baltimore), 9: 543, 1995.
36. Westerhof, G. R., Schornagel, J. H., Kathmann, I., Jackman, A. L., Rosowsky, A., Forsch, R. A., Hynes, J. B., Boyle, F. T., Peters, G. J., Pinedo, H. M., and Jansen, G. Carrier- and receptor-mediated transport of folate antagonists targeting folate-dependent enzymes: correlates of molecular-structure and biological activity. Mol. Pharmacol., 48: 459-471, 1995.
37. Rosowsky, A., Lazarus, H., Yuan, G. C., Beltz, W. R., Mangini, L., Abelson, H. T., Modest, E. J., and Frei, E. Effects of methotrexate esters and other lipophilic antifolates on methotrexate-resistant human leukemic lymphoblasts. Biochem. Pharmacol., 29: 648-652, 1980.
38. Mini, E., Moroson, B. A., Franco, C. T., and Bertino, J. R. Cytotoxic effects of folate antagonists against methotrexate-resistant human leukemic lymphoblast CCRF-CEM cell lines. Cancer Res., 45: 325-330, 1985.
39. Yalowich, J. C., and Kalman, T. I. Rapid determination of thymidylate synthase activity and its inhibition in intact L1210 leukemia cells in vitro. Biochem. Pharmacol., 34: 2319-2324, 1985.
40. Rodenhuis, S., McGuire, J. J., Narayanan, R., and Bertino, J. R. Development of an assay system for the detection and classification of methotrexate resistance in fresh human leukemic cells. Cancer Res., 46: 6513-6519, 1986.
41. Van Triest, B., Pinedo, H. M., Telleman, F., Van der Wilt, C. L., Jansen, G., and Peters, G. J. Cross-resistance to antifolates in multidrug resistant cell lines with P-glycoprotein or multidrug resistance protein expression. Biochem. Pharmacol., 53: 1855-1866, 1997.
42. Van der Wilt, C. L., Pinedo, H. M., Smid, K., and Peters, G. J. Elevation of thymidylate synthase following 5-fluorouracil treatment is prevented by the addition of leucovorin in murine colon tumors. Cancer Res., 52: 4922-4928, 1992.
43. Li, W. W., Lin, J. T., Chang, Y. M., Schweitzer, B., and Bertino, J. R. Prediction of antifolate efficacy in a rat sarcoma model. Int. J. Cancer, 49: 234-238, 1991.
44. 3H]2′-deoxyuridine and a clonogenic assay. Anticancer Res., 10: 759-764, 1990.
45. Yamauchi, H., Iwata, N., Omine, M., and Maekawa, T. In vitro methotrexate polyglutamate formation is elevated in acute lymphoid leukemia cells compared with acute myeloid leukemia and normal bone marrow cells. Acta Haematol. Jpn., 51: 766-773, 1988.
46. Longo, G. S., Gorlick, R., Tong, W. P., Ercikan, E., and Bertino, J. R. Disparate affinities of antifolates for folylpolyglutamate synthetase from human leukemia cells. Blood, 90: 1241-1245, 1997.
47. Jolivet, J. Biochemical and pharmacologic rationale for high-dose methotrexate. NCI Monogr., 5: 61-65, 1987.
48. Kamen, B. A., and Winick, N. J. High dose methotrexate therapy: insecure rationale? Biochem. Pharmacol., 37: 2713-2715, 1988.
49. Synold, T. W., Relling, M. V., Boyett, J. M., Rivera, G. K., Sandlund, J. T., Mahmoud, H., Crist, W. M., Pui, C. H., and Evans, W. E. Blast cell methotrexate-polyglutamate accumulation in vivo differs by lineage, ploidy, and methotrexate dose in acute lymphoblastic leukemia. J. Clin. Investig., 94: 1996-2001, 1994.
50. Smith, A., Hum, M., Winick, N. J., and Kamen, B. A. A case for the use of aminopterin in treatment of patients with leukemia based on metabolic studies of blasts in vitro. Clin. Cancer Res., 2: 69-73, 1996.
51. Hum, M. C., and Kamen, B. A. Folate, antifolates, and folate analogs in pediatric oncology. Investig. New Drugs, 14: 101-111, 1996.
52. Peters, G. J., and Ackland, S. P. New antimetabolites in preclinical and clinical development. Exp. Opin. Investig. New Drugs, 5: 637-679, 1995.
53. Cunninsham, D., Zalcberg, J. R., Rath, U., Oliver, I., Vancutsem, E., Svensson, C., Seitz, J. F., Harper, P., Kerr, D., and Perez-Manga, G. Final results of a randomised trial comparing Tomudex (Raltitrexed) with 5-fluorouracil plus leucovorin in advanced colorectal cancer. Tomudex Colorectal Cancer Study Group. Ann. Oncol., 7: 961-965, 1996.
54. Weitman, S., Carlson, L., and Pratt, C. B. New drug development for pediatric oncology. Investig. New Drugs, 14: 1-10, 1996.
55. Estlin, E. J., Ablett, S., Newell, D. R., Lewis, I. J., Lashford, L., and Pearson, A. D. Phase I trials in paediatric oncology: the European perspective. The New Agents Group of the United Kingdom Children's Cancer Study Group. Investig. New Drugs, 14: 23-32, 1996.
56. Sirotnak, F. M., Moccio, D. M., Goutas, L. J., Kelleher, L. E., and Montgomery, J. A. Biochemical correlates of responsiveness and collateral sensitivity of some methotrexate-resistant murine tumors to the lipophilic antifolate, metoprine. Cancer Res., 42: 924-928, 1982.
57. Mauritz, R., Kathmann, I., Pinedo, H. M., Peters, G. J., Jansen, G., Schornagel, J., Priest, D. G., Bunni, M., Drori, S., Sprecher, H., and Assaraf, Y. G. A novel mechanism of resistance to polyglutamatable antifolates in human CEM leukemia cells. In: W. Pfleiderer and H. Rokos (eds.), Chemistry and Biology of Pteridines and Folates, pp. 157-162. Berlin, Germany: Blackwell Science, 1997.
58. Chu, E., Drake, J. C., Boarman, D., Baram, J., and Allegra, C. J. Mechanism of thymidylate synthase inhibition by methotrexate in human neoplastic cell lines and normal human myeloid progenitor cells. J. Biol. Chem., 265: 8470-8478, 1990.
59. Rafi, I., Taylor, G. A., Calvete, J. A., Boddy, A. V., Balmanno, K., Bailey, N., Lind, M., Calvert, A. H., Webber, S., Jackson, R. C., Johnston, A., Clendeninn, N., and Newell, D. R. Clinical pharmacokinetic and pharmacodynamic studies with the nonclassical antifolate thymidylate synthase inhibitor 3,4-dihydro-2-amino-6-methyl-4-oxo-5-(4-pyridplthio)-quinazolone dihydrochloride (AG337) given by 24-h continuous intravenous infusion. Clin. Cancer Res., 1: 1275-1284, 1995.