Methotrexate resistance in relation to treatment outcome in childhood acute lymphoblastic leukemia

Journal of Hematology and Oncology

Volumn 8, Issue 1, 2015, Pages

  Wojtuszkiewicz, Anna ^a   Peters, Godefridus J ^b   Van Woerden, Nicole L ^a   Dubbelman, Boas ^a   Escherich, Gabriele ^c   Schmiegelow, Kjeld ^d,e   Sonneveld, Edwin ^f   Pieters, Rob ^f,g   Van De Ven, Peter M ^b   Jansen, Gerrit ^b   Assaraf, Yehuda G ^h   Kaspers, Gertjan J L ^a   Cloos, Jacqueline ^a,b  

^a University of Amsterdam   (Netherlands)

^b VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^c UNIVERSITY MEDICAL CENTER HAMBURG EPPENDORF   (Germany)

^d UNIVERSITY OF COPENHAGEN   (Denmark)

^e Rigshospitalet   (Denmark)

^f Dutch Childhood Oncology Group DCOG   (Netherlands)

^g Department of Radiation Oncology   (Netherlands)

^h TECHNION ISRAEL INSTITUTE OF TECHNOLOGY   (Israel)

Author keywords

Acute lymphoblastic leukemia; Antifolate; DHFR; Drug resistance; FPGS; Hyperdiploid; Methotrexate; RFC; TS

Indexed keywords

DIHYDROFOLATE REDUCTASE; FOLYLPOLYGLUTAMATE SYNTHASE; GAMMA GLUTAMYL HYDROLASE; METHOTREXATE; METHOTREXATE POLYGLUTAMATE; REDUCED FOLATE CARRIER; THYMIDYLATE SYNTHASE; POLYGLUTAMIC ACID;

ACUTE LYMPHOBLASTIC LEUKEMIA; ARTICLE; CANCER COMBINATION CHEMOTHERAPY; CANCER PROGNOSIS; CANCER SURVIVAL; CHILDHOOD LEUKEMIA; CHROMOSOME ABERRATION; CONTROLLED STUDY; DHFR GENE; DIAGNOSTIC TEST ACCURACY STUDY; DIPLOIDY; DRUG ACCUMULATION; DRUG CYTOTOXICITY; DRUG RESISTANCE; DRUG RESPONSE; DRUG SENSITIVITY; ENZYME ACTIVITY; ENZYME INHIBITION; EVENT FREE SURVIVAL; FPGH GENE; FPGS GENE; FUSION GENE; GENE EXPRESSION; GENE REARRANGEMENT; HUMAN; HUMAN CELL; IN VITRO STUDY; LYMPHOID PROGENITOR CELL; MAJOR CLINICAL STUDY; OVERALL SURVIVAL; PREDICTIVE VALUE; PROTEIN EXPRESSION; RFC GENE; SURVIVAL PREDICTION; SURVIVAL RATE; TEM AML1 GENE; TREATMENT OUTCOME; TS GENE; ADOLESCENT; ANALOGS AND DERIVATIVES; CHILD; FEMALE; MALE; PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA;

ADOLESCENT; CHILD; DRUG RESISTANCE, NEOPLASM; FEMALE; HUMANS; MALE; METHOTREXATE; POLYGLUTAMIC ACID; PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; TREATMENT OUTCOME;

EID: 84930668783     PISSN: None     EISSN: 17568722     Source Type: Journal    
DOI: 10.1186/s13045-015-0158-9     Document Type: Article

References (53)

1. Pui CH, Mullighan CG, Evans WE, Relling MV. Pediatric acute lymphoblastic leukemia: where are we going and how do we get there? Blood. 2012;120:1165-74.
2. Escherich G, Horstmann MA, Zimmermann M, Janka-Schaub GE. Cooperative study group for childhood acute lymphoblastic leukaemia (COALL): long-term results of trials 82,85,89,92 and 97. Leukemia. 2010;24:298-308.
3. Einsiedel HG, Von Stackelberg A, Hartmann R, Fengler R, Schrappe M, Janka-Schaub G, et al. Long-term outcome in children with relapsed ALL by risk-stratified salvage therapy: results of trial acute lymphoblastic leukemia-relapse study of the Berlin-Frankfurt-Munster Group 87. J Clin Oncol. 2005;23:7942-50.
4. Pui CH, Relling MV, Downing JR. Acute lymphoblastic leukemia. N Engl J Med. 2004;350:1535-48.
5. Meijerink JPP, den Boer ML, Pieters R. New genetic abnormalities and treatment response in acute lymphoblastic leukemia. Semin Hematol. 2009;46:16-23.
6. Bertino J. Karnofsky memorial lecture. Ode to methotrexate. J Clin Oncol. 1993;11:5-14.
7. Stokstad ELR. Historical perspectives on key advances in the biochemistry and physiology of folates. In: Picciano MF, Stokstad ELR, Gregory JF, editors. Evaluation of Folic Acid Metabolism in Health and Disease. New York, NY: Wiley-Liss; 1990. p. 1-21.
8. Cheok MH, Lugthart S, Evans WE. Pharmacogenomics of acute leukemia. Annu Rev Pharmacol Toxicol. 2006;46:317-53.
9. Assaraf YG. Molecular basis of antifolate resistance. Cancer Metastasis Rev. 2007;26:153-81.
10. Allegra CJ, Hoang K, Yeh GC, Drake JC, Baram J. Evidence for direct inhibition of de novo purine synthesis in human MCF-7 breast cells as a principal mode of metabolic inhibition by methotrexate. J Biol Chem. 1987;262:13520-6.
11. Allegra CJ, Chabner BA, Drake JC, Lutz R, Rodbard D, Jolivet J. Enhanced inhibition of thymidylate synthase by methotrexate polyglutamates. J Biol Chem. 1985;260:9720-6.
12. Baggott JE, Vaughn WH, Hudson BB. Inhibition of 5-aminoimidazole-4-carboxamide ribotide transformylase, adenosine deaminase and 5′-adenylate deaminase by polyglutamates of methotrexate and oxidized folates and by 5-aminoimidazole-4-carboxamide riboside and ribotide. Biochem J. 1986;236:193-200.
13. Gonen N, Assaraf YG. Antifolates in cancer therapy: structure, activity and mechanisms of drug resistance. Drug Resist Updat. 2012;15:183-210.
14. Hooijberg JH, Broxterman HJ, Kool M, Assaraf YG, Peters GJ, Noordhuis P, et al. Antifolate resistance mediated by the multidrug resistance proteins MRP1. Cancer Res. 1999;59:2532-5.
15. Masson E, Relling MV, Synold TW, Liu Q, Schuetz JD, Sandlund JT, et al. Accumulation of methotrexate polyglutamates in lymphoblasts is a determinant of antileukemic effects in vivo. J Clin Invest. 1996;97:73-80.
16. Kager L, Cheok M, Yang W, Zaza G, Cheng Q, Panetta JC, et al. Folate pathway gene expression differs in subtypes of acute lymphoblastic leukemia and influences methotrexate pharmacodynamics. J Clin Invest. 2005;115:110-7.
17. Rots MG, Pieters R, Peters GJ, Noordhuis P, van Zantwijk CH, Kaspers GJ, et al. Role of folylpolyglutamate synthetase and folylpolyglutamate hydrolase in methotrexate accumulation and polyglutamylation in childhood leukemia. Blood. 1999;93:1677-83.
18. Cheok MH, Pottier N, Kager L, Evans WE. Pharmacogenetics in acute lymphoblastic leukemia. Semin Hematol. 2009;46:39-51.
19. Rothem L, Aronheim A, Assaraf YG. Alterations in the expression of transcription factors and the reduced folate carrier as a novel mechanism of antifolate resistance in human leukemia cells. J Biol Chem. 2003;278:8935-41.
20. Rothem L, Stark M, Kaufman Y, Mayo L, Assaraf YG. Reduced folate carrier gene silencing in multiple antifolate-resistant tumor cell lines is due to a simultaneous loss of function of multiple transcription factors but not promoter methylation. J Biol Chem. 2004;279:374-84.
21. Kaufman Y, Ifergan I, Rothem L, Jansen G, Assaraf YG. Coexistence of multiple mechanisms of PT523 resistance in human leukemia cells harboring 3 reduced folate carrier alleles: transcriptional silencing, inactivating mutations, and allele loss. Blood. 2006;107:3288-94.
22. Schmiegelow K. Advances in individual prediction of methotrexate toxicity: a review. Br J Haematol. 2009;146:489-503.
23. De Jonge R, Hooijberg JH, van Zelst BD, Jansen G, van Zantwijk CH, Kaspers GJL, et al. Effect of polymorphisms in folate-related genes on in vitro methotrexate sensitivity in pediatric acute lymphoblastic leukemia. Blood. 2005;106:717-20.
24. Gregers J, Christensen IJ, Dalhoff K, Lausen B, Schroeder H, Rosthoej S, et al. The association of reduced folate carrier 80G> A polymorphism to outcome in childhood acute lymphoblastic leukemia interacts with chromosome 21 copy number. Blood. 2010;115:4671-7.
25. Mauritz R, Peters GJ, Priest DG, Assaraf YG, Drori S, Kathmann I, et al. Multiple mechanisms of resistance to methotrexate and novel antifolates in human CCRF-CEM leukemia cells and their implications for folate homeostasis. Biochem Pharmacol. 2002;63:105-15.
26. Zhao R, Titus S, Gao F, Moran RG, Goldman ID. Molecular analysis of murine leukemia cell lines resistant to 5, 10-dideazatetrahydrofolate identifies several amino acids critical to the function of folylpolyglutamate synthetase. J Biol Chem. 2000;275:26599-606.
27. Liani E, Rothem L, Bunni MA, Smith CA, Jansen G, Assaraf YG. Loss of folylpoly-gamma-glutamate synthetase activity is a dominant mechanism of resistance to polyglutamylation-dependent novel antifolates in multiple human leukemia sublines. Int J cancer. 2003;103:587-99.
28. Stark M, Wichman C, Avivi I, Assaraf YG. Aberrant splicing of folylpolyglutamate synthetase as a novel mechanism of antifolate resistance in leukemia. Blood. 2009;113:4362-9.
29. Whitehead VM, Vuchich MJ, Lauer SJ, Mahoney D, Carroll AJ, Shuster JJ, et al. Accumulation of high levels of methotrexate polyglutamates in lymphoblasts from children with hyperdiploid (greater than 50 chromosomes) B-lineage acute lymphoblastic leukemia: a Pediatric Oncology Group study. Blood. 1992;80:1316-23.
30. Belkov VM, Krynetski EY, Schuetz JD, Yanishevski Y, Masson E, Raimondi S, et al. Mechanism for ploidy but not lineage differences in methotrexate mechanism for ploidy but not lineage differences in methotrexate accumulation. Blood. 1999;93:1643-50.
31. Dervieux T, Hancock M, Evans W, Pui C, Relling M. Effect of methotrexate polyglutamates on thioguanine nucleotide concentrations during continuation therapy of acute lymphoblastic leukemia with mercaptopurine. Leukemia. 2002;16:209-12.
32. Schmiegelow K, Nielsen S, Frandsen TL, Nersting J. Mercaptopurine/methotrexate maintenance therapy of childhood acute lymphoblastic leukemia: clinical facts and fiction. J Pediatr Hematol Oncol. 2014;36:503-17.
33. Lennard L, Lilleyman JS, Van Loon J, Weinshilboum RM. Genetic variation in response to 6-mercaptopurine for childhood acute lymphoblastic leukaemia. Lance. 1990;336:225-9.
34. Rots MG, Pieters R, Kaspers GJ, van Zantwijk CH, Noordhuis P, Mauritz R, et al. Differential methotrexate resistance in childhood T- versus common/preB-acute lymphoblastic leukemia can be measured by an in situ thymidylate synthase inhibition assay, but not by the MTT assay. Blood. 1999;93:1067-74.
35. Rots M, Willey J, Jansen G, van Zantwijk CH, Noordhuis P, DeMuth J, et al. mRNA expression levels of methotrexate resistance-related proteins in childhood leukemia as determined by a standardized competitive template-based RT-PCR method. Leukemia. 2000;14:2166-75.
36. Synold TW, Relling MV, Boyett JM, Rivera GK, Sandlund JT, Mahmoud H, et al. Blast cell methotrexate-polyglutamate accumulation in vivo differs by lineage, ploidy, and methotrexate dose in acute lymphoblastic leukemia. J Clin Invest. 1994;94:1996-2001.
37. Whitehead VM, Rosenblatt DS, Vuchich MJ, Shuster JJ, Witte A, Beaulieu D. Accumulation of methotrexate and methotrexate polyglutamates in lymphoblasts at diagnosis of childhood acute lymphoblastic leukemia: a pilot prognostic factor analysis. Blood. 1990;76:44-9.
38. Whitehead VM, Shuster JJ, Vuchich MJ, Mahoney DH, Lauer SJ, Payment C, et al. Accumulation of methotrexate and methotrexate polyglutamates in lymphoblasts and treatment outcome in children with B-progenitor-cell acute lymphoblastic leukemia: a Pediatric Oncology Group study. Leukemia. 2005;19:533-6.
39. Levy AS, Sather HN, Steinherz PG, Sowers R, La M, Moscow JA, et al. Reduced folate carrier and dihydrofolate reductase expression in acute lymphocytic leukemia may predict outcome: a Children's Cancer Group Study. J Pediatr Hematol Oncol. 2003;25:688-95.
40. Kamps WA, van der Pal-de Bruin KM, Veerman AJP, Fiocco M, Bierings M, Pieters R. Long-term results of Dutch Childhood Oncology Group studies for children with acute lymphoblastic leukemia from 1984 to 2004. Leukemia. 2010;24:309-19.
41. Harms DO, Janka-Schaub GE. Co-operative study group for childhood acute lymphoblastic leukemia (COALL): long-term follow-up of trials 82, 85, 89 and 92. Leukemia. 2000;14:2234-9.
42. Jansen G, Mauritz R, Drori S, Sprecher H, Kathmann I, Bunni M, et al. A structurally altered human reduced folate carrier with increased folic acid transport mediates a novel mechanism of antifolate resistance. J Biol Chem. 1998;273:30189-98.
43. Galpin AJ, Schuetz JD, Masson E, Yanishevski Y, Synold TW, Barredo JC, et al. Differences in folylpolyglutamate synthetase and dihydrofolate reductase expression in human B-lineage versus T-lineage leukemic lymphoblasts: mechanisms for lineage differences in methotrexate polyglutamylation and cytotoxicity. Mol Pharmacol. 1997;52:155-63.
44. Wojtuszkiewicz A, Assaraf YG, Maas M, Kaspers G, Jansen G, Cloos J. Pre-mRNA splicing in cancer: the relevance in oncogenesis, treatment and drug resistance. Expert Opin Drug Metab Toxicol. 2015;11:673-89.
45. Roy K, Egan M, Sirlin S, Sirotnak F. Posttranscriptionally mediated decreases in folylpolyglutamate synthetase gene expression in some folate analogue-resistant variants of the L1210 Cell. J Biol Chem. 1997;272:6903-8.
46. Assaraf YG. The role of multidrug resistance efflux transporters in antifolate resistance and folate homeostasis. Drug Resist Updat. 2006;9:227-46.
47. Leclerc GJ, Sanderson C, Hunger S, Devidas M, Barredo JC. Folylpolyglutamate synthetase gene transcription is regulated by a multiprotein complex that binds the TEL-AML1 fusion in acute lymphoblastic leukemia. Leuk Res. 2010;34:1601-9.
48. Leclerc GJ, Mou C, Leclerc GM, Mian AM, Barredo JC. Histone deacetylase inhibitors induce FPGS mRNA expression and intracellular accumulation of long-chain methotrexate polyglutamates in childhood acute lymphoblastic leukemia: implications for combination therapy. Leukemia. 2010;24:552-62.
49. Veerman AJ, Kamps WA, van den Berg H, van den Berg E, Bökkerink JPM, Bruin MCA, et al. Dexamethasone-based therapy for childhood acute lymphoblastic leukaemia: results of the prospective Dutch Childhood Oncology Group (DCOG) protocol ALL-9 (1997-2004). Lancet Oncol. 2009;10:957-66.
50. Schmiegelow K, Forestier E, Hellebostad M, Heyman M, Kristinsson J, Söderhäll S, et al. Long-term results of NOPHO ALL-92 and ALL-2000 studies of childhood acute lymphoblastic leukemia. Leukemia. 2010;24:345-54.
51. Pieters R, Loonen AH, Huismans DR, Broekema G, Dirven M, Heyenbrok M, et al. In vitro drug sensitivity of cells from children with leukemia using the MTT assay with improved culture conditions. Blood. 1990;76:2327-36.
52. Kaspers GJ, Veerman AJ, Pieters R, Broekema GJ, Huismans DR, Kazemier KM, et al. Mononuclear cells contaminating acute lymphoblastic leukaemic samples tested for cellular drug resistance using the methyl-thiazol-tetrazolium assay. Br J Cancer. 1994;70:1047-52.
53. Mauritz R, Bekkenk M, Rots M, Pieters R, Mini E, van Zantwijk CH, et al. Ex vivo activity of methotrexate versus novel antifolate inhibitors of dihydrofolate reductase and thymidylate synthase against childhood leukemia cells. Clin Cancer Res. 1998;4:2399-410.