Analysis of the molecular determinants of the response of chronic myelogenous leukaemia to tyrosine kinase inhibitors

Current Pharmacogenomics

Volumn 5, Issue 3, 2007, Pages 201-213

  Labussière, Hélène ^a   Hayette, Sandrine ^b   Nicolini, Franck Emmanuel ^a  

^a EDOUARD HERRIOT HOSPITAL   (France)

^b CENTRE HOSPITALIER LYON SUD   (France)

Author keywords

BCR ABL; CML; Philadelphia chromosome; Tyrosine kinase inhibitors

Indexed keywords

ABELSON KINASE; ALPHA INTERFERON; BCR ABL PROTEIN; CYCLOPROPANECARBOXYLIC ACID [4 [4 (4 METHYL 1 PIPERAZINYL) 6 (5 METHYL 2H PYRAZOL 3 YLAMINO) 2 PYRIMIDINYLTHIO]PHENYL]AMIDE; CYTARABINE; DASATINIB; DAUNORUBICIN; HOMOHARRINGTONINE; IMATINIB; NILOTINIB; PLATELET DERIVED GROWTH FACTOR ALPHA RECEPTOR; PLATELET DERIVED GROWTH FACTOR BETA RECEPTOR; PREDNISONE; PROTEIN TYROSINE KINASE; PROTEIN TYROSINE KINASE INHIBITOR; STEM CELL FACTOR; VINCRISTINE;

ADVANCED CANCER; ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION; ANTINEOPLASTIC ACTIVITY; BLAST CELL CRISIS; CANCER CELL; CANCER CONTROL; CANCER SURVIVAL; CHRONIC MYELOID LEUKEMIA; CLINICAL TRIAL; CLONE; COMBINATION CHEMOTHERAPY; DISEASE COURSE; DISEASE FREE SURVIVAL; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG METABOLISM; DRUG PROTEIN BINDING; DRUG RESPONSE; DRUG STRUCTURE; DRUG TARGETING; DRUG TREATMENT FAILURE; GENE AMPLIFICATION; GENE MUTATION; HUMAN; LEUKEMIA RELAPSE; LONG TERM CARE; MOLECULAR MECHANICS; NONHUMAN; ONCOGENE; PHILADELPHIA 1 CHROMOSOME; POINT MUTATION; PROGNOSIS; RESERVOIR; REVIEW; STEM CELL; STRUCTURE ACTIVITY RELATION;

EID: 34648827221     PISSN: 15701603     EISSN: None     Source Type: Journal    
DOI: 10.2174/157016007781669231     Document Type: Review

References (75)

1. Abelson, H. T. and Rabstein, L. S. (1970) Lymphosarcoma: virus-induced thymic-independent disease in mice. Cancer Res. 30, 2213-2222.
2. Baccarani, M.; Stone, R.; Tura, S.; Fernandes-Reese, S.; Gathmann, I.; Capdeville, R.; Kantarjian, H. M. and Sawyers, C. L. (2002) Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study. Blood 99, 1928-1937.
3. Baccarani, M.; Saglio, G.; Goldman, J.; Hochhaus, A.; Simonsson, B.; Appelbaum, F.; Apperley, J.; Cervantes, F.; Cortes, J.; Deininger, M.; Gratwohl, A.; Guilhot, F.; Horowitz, M.; Hughes, T.; Kantarjian, H.; Larson, R.; Niederwieser, D.; Silver, R.; Hehlmann, R. and European LeukemiaNet. (2006) Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood 108, 1809-1820.
4. Barnes, D. J.; Schultheis, B.; Adedeji, S. and Melo, J. V. (2005) Dose-dependent effects of Bcr-Abl in cell line models of different stages of chronic myeloid leukemia. Oncogene 24, 6432-6440.
5. Bartram, C. R.; de Klein, A.; Hagemeijer, A.; van Agthoven, T.; Geurts van Kessel, A.; Bootsma, D.; Grosveld, G.; Ferguson-Smith, M. A.; Davies, T. and Stone, M. (1983) Translocation of c-abl oncogene correlates with the presence of a Philadelphia chromosome in chronic myelocytic leukaemia. Nature 306, 277-280.
6. Bedi, A.; Zehnbauer B. A.; Barber, J. P.; Sharkis, S. J. and Jones, R. J. (1994) Inhibition of apoptosis by BCR-ABL in chronic myeloid leukemia. Blood 83, 2038-2044.
7. Bhatia, R.; Wayner, E. A.; McGlave, P. B. and Verfaillie, C. M. (1994) Interferon-alpha restores normal adhesion of chronic myelogenous leukemia hematopoietic progenitors to bone marrow stroma by correcting impaired beta 1 integrin receptor function. J. Clin. Invest. 94, 384-391.
8. Bonifazi, F.; de Vivo, A.; Rosti, G.; Guilhot, F.; Guilhot, J.; Trabacchi, E.; Hehlmann, R.; Hochhaus, A.; Shepherd, P. C.; Steegmann, J. L.; Kluin-Nelemans, H. C.; Thaler, J.; Simonsson, B.; Louwagie, A.; Reiffers, J.; Mahon, F. -X.; Montefusco, E.; Alimena, G.; Hasford, J.; Richards, S.; Saglio, G.; Testoni, N.; Martinelli, G.; Tura, S. and Baccarani, M. (2001) European Study Group on Interferon in Chronic Myeloid Leukemia; Italian Cooperative Study Group on CML; France Intergroup of CML; German CML Study Group; UK Medical Research Council Working Party on CML; Spanish CML Study Group; Australian CML Study Group; Swedish CML Study Group. Chronic myeloid leukemia and interferon-alpha: a study of complete cytogenetic responders. Blood 98, 3074-3081.
9. Branford, S.; Rudzki, Z.; Walsh, S.; Grigg, A.; Arthur, C.; Taylor, K.; Herrmann, R.; Lynch, K. P. and Hughes, T. P. (2002) High frequency of point mutations clustered within the adenosine triphosphate-binding region of BCR/ABL in patients with chronic myeloid leukaemia or Ph-positive acute lymphoblastic leukaemia who develop imatinib (ST1571) resistance. Blood 99, 3472-3475.
10. Branford, S.; Rudzki, Z.; Walsh, S.; Parkinson, I.; Grigg, A.; Szer, J.; Taylor, K.; Hehlmann, R.; Seymour, J. F.; Arthur, C.; Joske, D.; Lynch, K. and Hughes, T. (2003) Detection of BCR-ABL in patients with CML treated with imatinib is virtually always accompanied by clinical resistance, and mutations in the ATP-binding loop (P-loop) are associated with a poor prognosis. Blood 102, 276-283.
11. Buchdunger, E.; Zimmermann, J.; Mett, H.; Meyer, T.; Müller, M.; Regenass, U. and Lydon, N. B. (1995) Selective inhibition of the platelet-derived growth factor signal transduction pathway by a protein-tyrosine kinase inhibitor of the 2-phenylaminopyrimidine class. Proc. Natl. Acad. Sci. USA 92, 2558-2562.
12. Buchdunger, E.; Zimmermann, J.; Mett, H.; Meyer, T.; Müller, M.; Druker, B. J. and Lydon, N. B. (1996) Inhibition of the Abl protein-tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative. Cancer Res. 56, 100-104.
13. Chu, S.; Xu, H.; Shah, N. P.; Snyder, D. S.; Forman, S. J.; Sawyers, C. L. and Bhatia, R. (2005) Detection of BCR-ABL kinase mutations in CD34+ cells from chronic myelogenous leukemia patients in complete cytogenetic remission on imatinib mesylate treatment. Blood 105, 2093-2098.
14. Copland, M.; Hamilton, A.; Elrick, L. J.; Baird, J. W.; Allan, E. K.; Jordanides, N.; Barow, M.; Mountford, J. C. and Holyoake, T. L. (2006) Dasatinib (BMS-354825) targets an earlier progenitor population than imatinib in primary CML but does not eliminate the quiescent fraction. Blood 107, 4532-4539.
15. Corbin, A. S.; Buchdunger, E.; Pascal, F. and Druker, D. J. (2002) Analysis of the structural basis of specificity of inhibition of the Abl kinase by STI571. J. Biol. Chem. 277, 32214-32219.
16. Corbin, A. S.; La Rosée, P.; Stoffregen, E. P.; Druker, B. J. and Deininger, M. W. (2003) Several Bcr-Abl kinase domain mutants associated with imatinib mesylate resistance remain sensitive to imatinib. Blood 101, 4611-4614.
17. Daley, G. Q.; Van Etten, R. A. and Baltimore, D. (1990) Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science 247, 824-830.
18. Deininger, M. W.; Goldman, J. M.; Lydon, N. and Meto, J. V. (1997) The tyrosine kinase inhibitor CGP57148B selectively inhibits the growth of BCR-ABL-positive cells. Blood 90, 3691-3698.
19. Donato, N. J.; Wu, J. Y.; Stapley, J.; Gallick, G.; Lin, H.; Arlinghaus, R. and Talpaz, M. (2003) BCR-ABL independence and LYN kinase overexpression in chronic myelogenous leukemia cells selected for resistance to ST1571. Blood 101, 690-698.
20. Druker, B. J.; Tamura, S.; Buchdunger, E.; Ohno, S.; Segal, G. M.; Fanning, S.; Zimmermann, J. and Lydon, N. B. (1996) Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat. Med. 2, 561-566.
21. Druker, B. J.; Talpaz, M.; Resta, D. J.; Peng, B.; Buchdunger, E.; Ford, J. M.; Lydon, N. B.; Kantarjian, H.; Capdeville, R.; Ohno-Jones, S. and Sawyers, C. L. (2001) Efficacy and salety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N. Engl. J. Med. 344, 1031-1037.
22. Druker, B. J.; Guilhot, F.; O'Brien, S. G.; Gathmann, I.; Kantarjian, H.; Gattermann, N.; Deininger, M. W. N.; Silver, R. T.; Goldman, J. M.; Stone, R. M.; Cervantes, F.; Hochhaus, A.; Powell, B. L.; Gabrilove, J. L.; Rousselot, P.; Reiffers, J.; Cornelissen, J. J.; Hughes, T.; Agis, H.; Fischer, T.; Verhoef, T.; Shepherd, J.; Saglio, G.; Gratwohl A.; Nielsen J. L.; Radich J. P.; Simonsson, B.; Taylor, K.; Baccarani, M.; So, C.; Letvak, L. and Larson, R. A. (2006) Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N. Engl. J. Med. 355, 2408-2417.
23. Gambacorti-Passerini, C.; le Coutre, P.; Mologni, L.; Fanelli, M.; Bertazzoli, C.; Marchesi, E.; Di Nicola, M.; Biondi, A.; Corneo, G. M.; Belotti, D.; Pogliani, E. and Lydon, N. B. (1997) Inhibition of the ABL kinase activity blocks the proliferation of BCR/ABL+ leukemic cells and induces apoptosis. Blood Cells Mol. Dis. 23, 380-394.
24. Gambacorti-Passerini, C.; Barni, R.; le Coutre, P.; Zucchetti, M.; Cabrita, G.; Cleris, L.; Rossi, F.; Gianazza, E.; Brueggen, J.; Cozens, R.; Pioltelli, P.; Pogliani, E.; Corneo, G.; Formelli, F. and D'Incalci, M. (2000) Role of alphal acid glycoprotein in the in vivo resistance of human BCR-ABL(+) leukemic cells to the abl inhibitor ST1571. J. Natl. Cancer Inst. 92, 1641-1650.
25. Gambacorti-Passerini, C. B.; Gunby, R. H.; Piazza, R.; Galietta, A.; Rostagno, R. and Scapozza, L. (2003) Molecular mechanisms of resistance to imatinib in Philadelphia-chromosome-positive leukaemias. Lancet Oncol. 4, 75-85.
26. Giles, F. J.; Cortes, J.; Jones, D.; Bergstrom, D.; Kantarjian, H. and Freedman, S. J. (2007) MK-0457, a novel kinase inhibitor, is active in patients with chronic myeloid leukaemia or acute lymphocytic leukaemia with the T3151 BCR-ABL mutation. Blood 109, 500-502.
27. Gorre, M. E.; Mohammed, M.; Ellwood, K.; Hsu, N.; Paquette, R.; Rao, P. N. and Sawyers, C. L. (2001) Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 293, 876-880.
28. Graham, S. M.; Jorgensen, H. G.; Allan, E.; Pearson, C.; Alcorn, M. J.; Richmond, L. and Holyoake, T. L. (2002) Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to ST1571 in vitro. Blood 99, 319-325.
29. Hayette, S.; Michallet, M.; Baille, M. -L.; Magaud, J. -P. and Nicolini, F. E. (2005) The Assessment and the Follow-up of the Proportion of T3151 Mutant Bcr-Abl Transcripts can Guide Adequate Therapeutic Strategy in CML Patient. Leuk. Res. 29, 1073-1077.
30. Heisterkamp, N.; Stephenson, J. R.; Groffen, J.; Hansen, P. F.; de Klein, A.; Bartram, C. R. and Grosveld, G. (1983) Localization of the c-abl oncogene adjacent to a translocation break point in chronic myelocytic leukaemia. Nature 306, 239-242.
31. Hochhaus, A.; Kreil, S.; Corbin, A. S.; La Rosée P.; Müller, M. C.; Lahaye, T.; Hanfstein, B.; Schoch, C.; Cross, N. C.; Berger, U.; Gschaidmeier, H.; Druker, B. J. and Hehlmann, R. (2002) Molecular and chromosomal mechanisms of resistance to imatinib (ST1571) therapy. Leukemia 16, 2190-2196.
32. Hochhaus, A. and La Rosée, P. (2004) Imatinib therapy in chronic myelogenous leukemia: strategies to avoid and overcome resistance. Leukemia 18, 1321-1231.
33. Holyoake, T.; Jiang, X.; Eaves, C. and Eaves, A. (1999) Isolation of a highly quiescent subpopulation of primitive leukemic cells in chronic myeloid leukemia. Blood 94, 2056-2064.
34. Holyoake, T. L.; Jiang, X.; Jorgensen, H. G.; Graham, S.; Alcorn, M. J.; Laird, C.; Eaves, A. C. and Eaves, C. J. (2001) Primitive quiescent leukemic cells from patients with chronic myeloid leukemia spontaneously initiate factor-independent growth in vitro in association with up-regulation of expression of interleukin-3. Blood 97, 720-728.
35. Hughes, T. P.; Kaeda, J.; Branford, S.; Rudzki, Z.; Hochhaus, A.; Hensley, M. L.; Gathmann, I.; Bolton A. E.; van Hoomissen, I. C.; Goldman, J. M.; Radich, J. P. and International Randomised Study of Interferon versus STT571 (IRIS) Study Group, (2003) Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. N. Engl. J. Med. 349, 1423-1432.
36. Hughes,T. P.; Deininger, M.; Hochhaus, A.; Branford, S.; Radich, J.; Kaeda, J.; Baccarani, M.; Cortes, J.; Cross, N. C.; Druker, B. J.; Gabert, J.; Grimwade, D.; Hehlmann, R.; Kamel-Reid, S.; Lipton, J. H.; Longtine, J.; Martinelli, G.; Saglio, G.; Soverini, S.; Stock, W. and Goldman, J. M. (2006) Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood 108, 28-37.
37. Illmer, T.; Schaich, M.; Platzbecker, U.; Freiberg-Richter, J.; Oelschlagel, U.; von Bonin, M.; Pursche S.; Bergemann, T.; Ehninger, G. and Schleyer, E. (2004) P-glycoprotein-mediated drug efflux is a resistance mechanism of chronic myelogenous leukemia cells to treatment with imatinib mesylate. Leukemia 18, 401-408.
38. Jabbour, E.; Kantarjian, H.; Jones, D.; Talpaz, M.; Bekele, N.; O'Brien, S.; Zhou, X.; Garcia-Manero, G.; Giles, F.; Rios, M. B.; Verstovsek, S. and Cortes, J. (2006) Frequency and clinical significance of BCR-ABL mutations in patients with chronic myeloid leukemia treated with imatinib mesylate. Leukemia 21, 1767-1773.
39. Jordanides, N. E.; Jorgensen, H. G.; Holyoake, T. L. and Mountford, J. C. (2006) Functional ABCG2 is overexpressed on primary CML CD34+ cells and is inhibited by imatinib mesylate. Blood 108, 1370-1373.
40. Kantarjian, H.; Giles, F.; Wunderle, L.; Bhalla, K.; O'Brien, S.; Wassmann, B.; Tanaka, C.; Manley, P.; Rae, P.; Mietlowski, W.; Bochinski, K.; Hochhaus, A.; Griffin, J. D.; Hoelzer, D.; Albitar, M.; Dugan, M.; Cortes, J.; Alland, L. and Ottmann, O. G. (2006) Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N. Engl. J. Med. 354, 2542-2551.
41. Kasper, B.; Fruehauf, S.; Schiedlmeier, B.; Buchdunger, E.; Ho, A. D. and Zeller, W. J. (1999) Favorable therapeutic index of a p210(BCR-ABL)-specific tyrosine kinase inhibitor; activity on lineage-committed and primitive chronic myelogenous leukemia progenitors. Cancer Chemother. Pharmacol. 44, 433-438.
42. le Coutre, P.; Mologni, L.; Cleris, L.; Marchesi, E.; Buchdunger, E.; Giardini, R.; Formelli, F. and Gambacorti-Passerini, C. (1999) In vivo eradication of human BCR/ABL-positive leukemia cells with an ABL kinase inhibitor. J. Natl. Cancer Inst. 91, 163-168.
43. le Coutre, P.; Tassi, E.; Varella-Garcia, M.; Barni, R.; Mologni, L.; Cabrita, G.; Marchesi, E.; Supino, R. and Gambacorti-Passerini, C. (2000) Induction of resistance to the Abelson inhibitor ST1571 in human leukemic cells through gene amplification. Blood 95, 1758-1766.
44. Lombardo, L. J.; Lee, F. Y.; Chen, P.; Norris, D.; Barrish, J. C.; Behnia, K.; Castaneda, S.; Cornelius, L. A.; Das, J.; Doweyko, A. M.; Fairchild, C.; Hunt, J. T.; Inigo, I.; Johnston, K.; Kamath, A.; Kan, D.; Klei, H.; Marathe, P.; Pang, S.; Peterson, R.; Pitt, S.; Schieven, G. L.; Schmidt, R. J.; Tokarski, J.; Wen, M. L.; Wityak, J. and Borzilleri, R. M. (2004) Discovery of N-(2-chloro-6-methyl- phenyl)-2-(6-(4-(2-hydroxyethyl)-piperaxin-1-yl)-2-methylpyrimidin- 4-ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays. J. Med. Chem. 47, 6658-6661.
45. Lugo T. G.; Pendergast, A. M.; Muller, A. J. and Witte, O. N. (1990) Tyrosine kinase activity and transformation potency of bcr-abl oncogene products. Science 247, 1079-1082.
46. Mahon, F. -X.; Deininger, M. W.; Schultheis, B.; Chabrol, J.; Reiffers, J.; Goldman, J. M. and Melo, J. V. (2000) Selection and characterization of BCR-ABL positive cell lines with differential sensitivity to the tyrosine kinase inhibitor ST1571: diverse mechanisms of resistance. Blood 96, 1070-1079.
47. Mahon, F. -X.; Belloc, F.; Lagarde, V.; Chollet, C.; Moreau-Gaudry, F.; Reiffers, J.; Goldman, J. M. and Melo, J. V. (2003) MDR1 gene overexpression confers resistance to imatinib mesylate in leukemia cell line models. Blood 101, 2368-2373.
48. Martin, G. S. (2004) The road to Src. Oncogene 23, 7910-7917.
49. Nagar, B.; Bommann, W. G.; Pellicena, P.; Schindler, T.; Veach, D. R.; Miller, W. T.; Clarkson, B. and Kuriyan, J. (2002) Crystal structures of the kinase domain of c-Abl in complex with the small molecule inhibitors PD173955 and imatinib (STI-571). Cancer Res. 62, 4236-4243.
50. Nicolini, F. E.; Corm, S.; Lê, Q. -H.; Sorel, N.; Hayette, S.; Bories, D.; Leguay, T.; Roy, L.; Giraudier, S.; Tulliez, M.; Facon, T.; Mahon, F. -X.; Cayuela, J. -M.; Rousselot, P.; Michallet, M.; Preudhomme, C.; Guilhot, F. and Roche-Lestienne, C. (2006) Mutation status of 89 imatinib mesylate resistant chronic myelogenous leukemia patients and clinical outcome. A retrospective analysis from the french intergroup of CML (Fi(Phi)-LMC group). Leukemia 20, 1061-1066.
51. Nicolini, F. E.; Corm, S.; Lê, Q. -H.; Roche-Lestienne, C. and Preudhomme, C. (2007a) The prognosis impact of BCR-ABL P-loop mutations: Worse or not worse? Leukemia 21, 193-194.
52. Nicolini, F. E.; Chabane, K.; Tigaud, I.; Michallet, M.; Magaud, J. -P. and Hayette, S. (2007) BCR-ABL mutant kinetics in CML patients treated with dasatinib. Leuk. Res. 31(6), 865-868.
53. Nowell, P. C. and Hungerford, D. A. (1960) Chromosome studies on normal and leukemic human leukocytes. J. Natl. Cancer Inst. 25, 85-109.
54. O'Brien, S. G.; Guilhot, F.; Larson, R. A.; Gathmann, I.; Baccarani, M.; Cervantes, F.; Cornelissen, J. J.; Fischer, T.; Hochhaus, A.; Hughes, T.; Lechner, K.; Nielsen, J. L.; Rousselot, P.; Reiffers, J.; Saglio, G.; Shepherd, J.; Simonsson, B.; Gratwohl, A.; Goldman, J.; Kantarjian, H.; Taylor, K.; Verhoef, G.; Bolton, A. E.; Capdevilie, R. and Druker, B. J. (2003) Imatinib compared with Interferon and low-dose cytarabine for newly diagnosed chronic mycloid leukaemia. N. Engl. J. Med. 348, 994-1004.
55. O'Hare, T.; Walters, D. K.; Stoffregen, E. P.; Jia, T.; Manley, P. W.; Mestan, J.; Cowan-Jacob, S. W.; Lee, F. Y.; Heinrich, M. C.; Deininger, M. W. N. and Druker, B. J. (2005) In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants. Cancer Res. 65, 4500-4505.
56. Picard, S.; Titier, K.; Etienne, G.; Teilhet, E.; Ducint, D.; Bernard, M. -A.; Lassale, R.; Marit, G.; Reiffers, J.; Begaud, B.; Moore, N.; Molimard, M. and Mahon, F. -X. (2007) Trough plasma levels are associated with both cytogenetic and molecular responses to standard-dose imatinib in chronic myeloid leukaemia. Blood 109, 3496-3499.
57. Roche-Lestienne, C.; Soenen-Cornu, V.; Grardel-Duflos, N.; Lai, J. L.; Philippe, N.; Facon, T.; Fenaux, P. and Preudhomme, C. (2002) Several types of mutations of the Abl gene can be found in chronic myeloid leukemia patients resistant to STI 571, and they can preexist to the onset of treatment. Blood100, 1014-1018.
58. Roumantsiev, S.; Shah, N. P.; Gorre, M. E.; Nicoll, J.; Brasher, B. B.; Sawyers, C. L. and Van Etten, R. A. (2002) Clinical resistance to the kinase inhibitor ST1-571 in chronic myeloid leukaemia by mutation of Tyr-253 in the Abl kinase domain P-loop. Proc. Natl. Acad. Sci. USA 99, 10700-10705.
59. Rowley, J. D. (1973) A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 243, 290-293.
60. Savage, D. G. and Goldman, J. M. (1997) Allograffing for chronic myeloid laukemia. Curr. Opin. Hematol. 4, 369-376.
61. Sawyers, C. L.; Hochhaus, A.; Feldman, E.; Goldman, J. M.; Miller, C. B.; Ottmann, O. G.; Schiffer, C. A.; Talpaz, M.; Guilhot, F.; Deininger, M. W.; Fischer, T.; O'Brien, S. G.; Stone, R. M.; Gambacorti-Passerini, C. B.; Russell, N. H.; Reiffers, J.; Shea, T. C.; Chapuis, B.; Coutre, S.; Tura, S.; Morra, E.; Larson, R. A.; Saven, A.; Peschel, C.; Gratwohl, A.; Mandelli, F.; Ben-Am, M.; Gathmann, I.; Capdeville, R.; Paquette, R. L. and Druker, B. J. (2002) Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study. Blood 99, 3530-3539.
62. Shah, N. P.; Nicoll, J. M.; Nagar, B.; Gorre, M. E.; Paquette, R. L.; Kuriyan, J. and Sawyers, C. L. (2002) Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis chronic myeloid leukemia. Cancer Cell 2, 117-125.
63. Shah, N. P.; Tran, C.; Lee, F. Y.; Chen, P.; Norris, D. and Sawyers, C. L. (2004) Overriding imatinib resistance with a novel ABL kinase inhibitor. Science 305, 399-401.
64. Skaggs, B. J.; Gorre, M. E.; Ryvkin, A.; Burgess, M. R.; Xie, Y.; Han, Y.; Komisopoulou, E.; Brown, L. M.; Loo, J. A.; Landaw, E. M.; Sawyers, C. L. and Graeber, T. G. (2006) Phosphorylation of the ATP-binding loop directs oncogenicity of drug-resistant BCR-ABL mutants. Proc. Natl. Acad. Sci. USA 103, 19466-19471.
65. Smith, P. F.; Bullock, J. M.; Booker, B. M.; Haas, C. E.; Berenson, C. S. and Jusko, W. J. (2004) Induction of imatinib metabolism by hypericum perforatum. Blood 104, 1229-1230.
66. Soverini, S.; Martinelli, G.; Rosti, G.; Bassi, S.; Amabile, M.; Poerio, A.; Gianini, B.; Trabacchi, E.; Castagnetti, F.; Testoni, N.; Luatti, S.; de Vivo, A.; Cilloni, D.; Izzo, B.; Fava, M.; Abruzzese, M.; Alberti, D.; Pane, F.; Saglio, G. and Baccarani, M. (2005) ABL mutations in late chronic phase chronic myeloid leukaemia patients with up-front cytogenetic resistance to imatinib are associated with a greater likelihood of progression to blast crisis and shorter survival: A study from the GIMEMA working party on chronic myeloid leukaemia. J. Clin. Oncol. 23, 4100-4109.
67. Talpaz, M.; Kantarjian, H.; Kurzrock, R.; Trujillo, J. M. and Gutterman, J. U. (1991) Interferon-alpha produces sustained cylogenetic responses in chronic myelogenous leukemia. Philadelphia chromosome-positive patients. Ann. Intern. Med. 114, 532-538.
68. Talpaz, M.; Silver, R. T.; Druker, B. J.; Goldman, J. M.; Gambacorti-Passerini, C.; Guilhot, F.; Schiffer, C. A.; Fischer, T.; Deininger, M. W.; Lennard, A. L.; Hochhaus, A.; Ottmann, O. G.; Gratwohl, A.; O'Brien, S.; Guilhot, F.; Larson, R. A.; Gathmann, I.; Baccarani, M.; Cervantes, F.; Cornelissen, J. J.; Fischer, T.; Hochhaus, A.; Hughes, T.; Lechner, K.; Nielsen, J. L.; Rousselot, P.; Reiffers, J.; Saglio, G.; Shepherd, J.; Simonsson, B.; Gratwohl, A.; Goldman, J. M.; Kantarjian, H.; Taylor, K.; Verhoed, G.; Bolton, A. E.; Capdeville, R. and Druker, B. J. (2003) Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N. Engl. J. Med. 348, 994-1004.
69. Talpaz, M.; Shah, N. P.; Kantarjian, H.; Donato, N.; Nicoll, J.; Paquette, R.; Cortes, J.; O'Brien, S.; Nicaise, C.; Bleickardt, E.; Blackwood-Chirchir, A.; Iyer, V.; Chen, T. -T.; Huang, F.; Decillis, A. P. and Sawyers, C. L. (2006) Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N. Engl. J. Med. 354, 2531-2541.
70. Thomas, J.; Wang, L.; Clark, R. E. and Pirmohamed, M, (2004) Active transport of imatinib into and out of cells: implications for drug resistance. Blood 104, 3739-3745.
71. von Bubnoff, N.; Schneller, F.; Peschel, C. and Duyster, L. (2002) BCR-ABL gene mutations in relation to clinical resistance of Philadelphia-chromosome-positive leukaemia to ST1571: a prospective study. Lancet 359, 487-491.
72. Warmuth, M.; Bergmann, M.; Priess, A.; Hauslmann, K.; Emmerich, B. and Hallek, M. (097) The Src family kinase Hck interacts with Bcr-Abl by a kinase-independent mechanism and phosphorylates the Grb2-binding site of Bcr. J. Biol. Chem. 272, 33260-33270.
73. White, D. L., Saunders, V.A.; Dang, P.; Engler, J.; Zannettino, A. C.; Cambareri, A. C.; Quinn, S. R.; Manley, P. W. and Hugbes, T. P. (2006) OCT-1-mediated influx is a key determinant of the intracellular uptake of imatinib but not nilotinib (AMN107): reduced OCT-1 activity is the cause of low in vitro sensitivity to imatinib. Blood 108, 697-704.
74. Weisberg, E. and Griffin, J. D. (2000) Mechanism,of resistance to the ABL tyrosine kinase inhibitor ST1571 in BCR/ABL-transformed hematopoietic cell lines. Blood 95, 3498-3505.
75. Weisberg, E.; Manley, P. W.; Breitenstein, W.; Bruggen, J.; Cowan-Jacob, S. W.; Ray, A.; Huntly, B.; Fabbro, D.; Fendrich, G.; Hall-Meyers, E.; Kung, A. L.; Mestan, J.; Daley, G. Q.; Callahan, L.; Catley, L.; Cavazza, C.; Azam, M.; Neuberg, D.; Wright, R. D.; Gilliland, D., G. and Griffin, J. D. (2005) Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl. Cancer Cell 7, 129-141.