BCR-ABL residues interacting with ponatinib are critical to preserve the tumorigenic potential of the oncoprotein

FASEB Journal

Volumn 28, Issue 3, 2014, Pages 1221-1236

  Buffa, Pietro ^a   Romano, Chiara ^b   Pandini, Alessandro ^a   Massimino, Michele ^b   Tirrò, Elena ^b   Di Raimondo, Francesco ^b   Manzella, Livia ^b   Fraternali, Franca ^a   Vigneri, Paolo G ^b,c  

^a KING'S COLLEGE LONDON   (United Kingdom)

^b UNIVERSITY OF CATANIA   (Italy)

^c ISTITUTO SUPERIORE DI SANITÀ   (Italy)

Author keywords

CML; Molecular dynamics; Mutations; Resistance; TKIs

Indexed keywords

ABELSON KINASE; ADENOSINE TRIPHOSPHATE; AMINO ACID; ARGININE; ASPARTIC ACID; BCR ABL PROTEIN; BRAIN DERIVED NEUROTROPHIC FACTOR RECEPTOR; DASATINIB; EPHRIN RECEPTOR; FIBROBLAST GROWTH FACTOR RECEPTOR 1; FIBROBLAST GROWTH FACTOR RECEPTOR 2; FIBROBLAST GROWTH FACTOR RECEPTOR 3; FIBROBLAST GROWTH FACTOR RECEPTOR 4; GLUTAMIC ACID; HEMATOPOIETIC CELL KINASE; IMATINIB; INTERLEUKIN 3; ISOLEUCINE; METHIONINE; NEUROTROPHIN 3 RECEPTOR; ONCOPROTEIN; PONATINIB; PROTEIN KINASE FYN; PROTEIN KINASE LCK; PROTEIN KINASE LYN; PROTEIN KINASE YES; PROTEIN KINASE ZAP 70; PROTEIN RET; PROTEIN TYROSINE KINASE A; VASCULOTROPIN RECEPTOR 1; IMIDAZOLE DERIVATIVE; PRIMER DNA; PYRIDAZINE DERIVATIVE;

ALPHA HELIX; AMINO ACID SUBSTITUTION; ARTICLE; CARCINOGENESIS; CELL PROLIFERATION; CELL SURVIVAL; CHRONIC MYELOID LEUKEMIA; CONFORMATIONAL TRANSITION; ENZYME ACTIVE SITE; ENZYME INHIBITOR INTERACTION; GENE MUTATION; GENETIC TRANSFECTION; HELIX ALPHA C; HUMAN; HUMAN CELL; HYDROGEN BOND; IMMUNOBLOTTING; IN VITRO STUDY; MOLECULAR DYNAMICS; POINT MUTATION; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN PHOSPHORYLATION; PROTEIN STABILITY; PROTEIN STRUCTURE; SEQUENCE ALIGNMENT; BIOCATALYSIS; CELL LINE; CML; METABOLISM; MUTATIONS; NUCLEOTIDE SEQUENCE; RESISTANCE; TKIS;

CML; MOLECULAR DYNAMICS; MUTATIONS; RESISTANCE; TKIS;

BASE SEQUENCE; BIOCATALYSIS; CELL LINE; DNA PRIMERS; FUSION PROTEINS, BCR-ABL; HUMANS; IMIDAZOLES; PYRIDAZINES;

EID: 84899509533     PISSN: 08926638     EISSN: 15306860     Source Type: Journal    
DOI: 10.1096/fj.13-236992     Document Type: Article

References (67)

1. Goldman, J. M., and Melo, J. V. (2003) Chronic myeloid leukemia -Advances in biology and new approaches to treatment. N. Engl. J. Med. 349, 1451-1464
2. Melo, J. V., and Barnes, D. J. (2007) Chronic myeloid leukaemia as a model of disease evolution in human cancer. Nat. Rev. Cancer 7, 441-453
3. Deininger, M., O'Brien, S. G., Guilhot, F., Goldman, J. M., Hochhaus, A., Hughes, T. P., Radich, J. P., Hatfield, A. K., Mone, M., Filian, J., Reynolds, J., Gathmann, I., Larson, R. A., and Druker, B. J. (2009) International Randomized Study of Interferon vs STI571 (IRIS) 8-year follow up: sustained survival and low risk for progression or events in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CMLCP) treated with imatinib. Blood (ASH Annu. Meet. Abstr.) 114, 1126
4. Kantarjian, H. M., Talpaz, M., Giles, F., O'Brien, S., and Cortes, J. (2006) New insights into the pathophysiology of chronic myeloid leukemia and imatinib resistance. Ann. Intern. Med. 145, 913-923
5. Druker, B. J. (2008) Translation of the Philadelphia chromosome into therapy for CML. Blood 112, 4808-4817
6. 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
7. Aloisi, A., Di Gregorio, S., Stagno, F., Guglielmo, P., Mannino, F., Sormani, M. P., Bruzzi, P., Gambacorti-Passerini, C., Saglio, G., Venuta, S., Giustolisi, R., Messina, A., and Vigneri, P. (2006) BCR-ABL nuclear entrapment kills human CML cells: ex vivo study on 35 patients with the combination of imatinib mesylate and leptomycin B. Blood 107, 1591-1598
8. 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
9. O'Hare, T., Shakespeare, W. C., Zhu, X., Eide, C. A., Rivera, V. M., Wang, F., Adrian, L. T., Zhou, T., Huang, W.-S., Xu, Q., Metcalf, C. A., Tyner, J. W., Loriaux, M. M., Corbin, A. S., Wardwell, S., Ning, Y., Keats, J. A., Wang, Y., Sundaramoorthi, R., Thomas, M., Zhou, D., Snodgrass, J., Commodore, L., Sawyer, T. K., Dalgarno, D. C., Deininger, M. W. N., Druker, B. J., and Clackson, T. (2009) AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell 16, 401-412
10. Jabbour, E., Jones, D., Kantarjian, H. M., O'Brien, S., Tam, C., Koller, C., Burger, J. A., Borthakur, G., Wierda, W. G., and Cortes, J. E. (2009) Long-Term outcome of patients with chronic myeloid leukemia treated with second-generation tyrosine kinase inhibitors after imatinib failure is predicted by the in vitro sensitivity of BCR-ABL kinase domain mutations. Blood 114, 2037-2043
11. Cortes, J. E., Kantarjian, H., Shah, N. P., Bixby, D., Mauro, M. J., Flinn, I., O'Hare, T., Hu, S., Narasimhan, N. I., Rivera, V. M., Clackson, T., Turner, C. D., Haluska, F. G., Druker, B. J., Deininger, M. W., and Talpaz, M. (2012) Ponatinib in refractory Philadelphia chromosome-positive leukemias. N. Engl. J. Med. 367, 2075-2088
12. Apperley, J. F. (2007) Part I: mechanisms of resistance to imatinib in chronic myeloid leukaemia. Lancet Oncol. 8, 1018-1029
13. Jabbour, E., Branford, S., Saglio, G., Jones, D., Cortes, J. E., and Kantarjian, H. M. (2011) Practical advice for determining the role of BCR-ABL mutations in guiding tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia. Cancer 117, 1800-1811
14. Quintas-Cardama, A., Kantarjian, H., and Cortes, J. (2009) Imatinib and beyond -exploring the full potential of targeted therapy for CML. Nat. Rev. Clin. Oncol. 6, 535-543
15. Ernst, T., and Hochhaus, A. (2012) Chronic myeloid leukemia: clinical impact of BCR-ABL1 mutations and other lesions associated with disease progression. Semin. Oncol. 39, 58-66
16. 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
17. Gibbons, D. L., Pricl, S., Kantarjian, H., Cortes, J., and Quintás-Cardama, A. (2012) The rise and fall of gatekeeper mutations? The BCR-ABL1 T315I paradigm. Cancer 118, 293-299
18. Nicolini, F. E., Ibrahim, A. R., Soverini, S., Martinelli, G., Muller, M. C., Hochhaus, A., Dufva, I. H., Kim, D. W., Cortes, J., Mauro, M. J., Chuah, C., Labussiere, H., Morisset, S., Roche-Lestienne, C., Lippert, E., Hayette, S., Peter, S., Zhou, W., Maguer-Satta, V., Michallet, M., Goldman, J., Apperley, J. F., Mahon, F. O., Marin, D., and Etienne, G. (2013) The BCR-ABLT315I mutation compromises survival in chronic phase chronic myelogenous leukemia patients resistant to tyrosine kinase inhibitors, in a matched pair analysis. Haematologica 98, 1510-1516
19. Lovera, S., Sutto, L., Boubeva, R., Scapozza, L., Dölker, N., and Gervasio, F. L. (2012) The different flexibility of c-Src and c-Abl kinases regulates the accessibility of a druggable inactive conformation. J. Am. Chem. Soc. 134, 2496-2499
20. Shan, Y., Seeliger, M. A., Eastwood, M. P., Frank, F., Xu, H., Jensen, M. O., Dror, R. O., Kuriyan, J., and Shaw, D. E. (2009) A conserved protonation-dependent switch controls drug binding in the Abl kinase. Proc. Natl. Acad. Sci. U. S. A. 106, 139-144
21. Levinson, N. M., Kuchment, O., Shen, K., Young, M. A., Koldobskiy, M., Karplus, M., Cole, P. A., and Kuriyan, J. (2006) A Src-like inactive conformation in the abl tyrosine kinase domain. PLoS Biol. 4, e144
22. Aleksandrov, A., and Simonson, T. (2010) Molecular dynamics simulations show that conformational selection governs the binding preferences of imatinib for several tyrosine kinases. J. Biol. Chem. 285, 13807-13815
23. Verkhivker, G. M. (2007) In silico profiling of tyrosine kinases binding specificity and drug resistance using Monte Carlo simulations with the ensembles of protein kinase crystal structures. Biopolymers 85, 333-348
24. Lin, Y. L., Meng, Y., Jiang, W., and Roux, B. (2013) Explaining why Gleevec is a specific and potent inhibitor of Abl kinase. Proc. Natl. Acad. Sci. U. S. A. 110, 1664-1669
25. Dixit, A., and Verkhivker, G. M. (2009) Hierarchical modeling of activation mechanisms in the ABL and EGFR kinase domains: thermodynamic and mechanistic catalysts of kinase activation by cancer mutations. PLoS Comput. Biol. 5, e1000487
26. Dixit, A., and Verkhivker, G. M. (2011) Computational modeling of allosteric communication reveals organizing principles of mutation-induced signaling in ABL and EGFR kinases. PLoS Comput. Biol. 7, e1002179
27. Lee, T.-S., Ma, W., Zhang, X., Giles, F., Cortes, J., Kantarjian, H., and Albitar, M. (2008) BCR-ABL alternative splicing as a common mechanism for imatinib resistance: evidence from molecular dynamics simulations. Mol. Cancer Ther. 7, 3834-3841
28. Lee, T.-S., Potts, S. J., and Albitar, M. (2009) Basis for resistance to imatinib in 16 BCR-ABL mutants as determined using molecular dynamics. Recent Pat. Anticancer Drug Discov. 4, 164-173
29. Lee, T.-S., Potts, S. J., Kantarjian, H., Cortes, J., Giles, F., and Albitar, M. (2008) Molecular basis explanation for imatinib resistance of BCR-ABL due to T315I and P-loop mutations from molecular dynamics simulations. Cancer 112, 1744-1753
30. Pricl, S., Fermeglia, M., Ferrone, M., and Tamborini, E. (2005) T315I-mutated Bcr-Abl in chronic myeloid leukemia and imatinib: insights from a computational study. Mol. Cancer Ther. 4, 1167-1174
31. Zhou, T., Commodore, L., Huang, W.-S., Wang, Y., Thomas, M., Keats, J., Xu, Q., Rivera, V. M., Shakespeare, W. C., Clackson, T., Dalgarno, D. C., and Zhu, X. (2011) Structural mechanism of the Pan-BCR-ABL inhibitor ponatinib (AP24534): lessons for overcoming kinase inhibitor resistance. Chem. Biol. Drug Des. 77, 1-11
32. Nagar, B., Bornmann, 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
33. Tokarski, J. S., Newitt, J. A., Chang, C. Y. J., Cheng, J. D., Wittekind, M., Kiefer, S. E., Kish, K., Lee, F. Y. F., Borzillerri, R., Lombardo, L. J., Xie, D., Zhang, Y., and Klei, H. E. (2006) The structure of dasatinib (BMS-354825) bound to activated ABL kinase domain elucidates its inhibitory activity against imatinib-resistant ABL mutants. Cancer Res. 66, 5790-5797
34. Preyer, M., Vigneri, P., and Wang, J. Y. (2011) Interplay between kinase domain autophosphorylation and F-Actin binding domain in regulating imatinib sensitivity and nuclear import of BCR-ABL. PLoS One 6, e17020
35. Sali, A., and Blundell, T. L. (1993) Comparative protein modelling by satisfaction of spatial restraints. J. Mol. Biol. 234, 779-815
36. Bernstein, F. C., Koetzle, T. F., Williams, G. J., Meyer, E. F., Brice, M. D., Rodgers, J. R., Kennard, O., Shimanouchi, T., and Tasumi, M. (1977) The Protein Data Bank: a computer-based archival file for macromolecular structures. J. Mol. Biol. 112, 535-542
37. Cowan-Jacob, S. W., Fendrich, G., Floersheimer, A., Furet, P., Liebetanz, J., Rummel, G., Rheinberger, P., Centeleghe, M., Fabbro, D., and Manley, P. W. (2007) Structural biology contributions to the discovery of drugs to treat chronic myelogenous leukaemia. Acta Crystallogr. D Biol. Crystallogr. 63, 80-93
38. Van der Spoel, D., Lindahl, E., Hess, B., Groenhof, G., Mark, A. E., and Berendsen, H. J. C. (2005) GROMACS: fast, flexible, and free. J. Comput. Chem. 26, 1701-1718
39. Sorin, E. J., and Pande, V. S. (2005) Exploring the helix-coil transition via all-Atom equilibrium ensemble simulations. Biophys. J. 88, 2472-2493
40. Hornak, V., Abel, R., Okur, A., Strockbine, B., Roitberg, A., and Simmerling, C. (2006) Comparison of multiple Amber force fields and development of improved protein backbone parameters. Proteins 65, 712-725
41. Jorgensen, W., Chandrasekhar, J., Madura, J., Impey, R., and Klein, M. (1983) Comparison of simple potential functions for simulating liquid water. J. Chem. Phys. 79, 926
42. Wang, J., Wolf, R. M., Caldwell, J. W., Kollman, P. A., and Case, D. A. (2004) Development and testing of a general amber force field. J. Comput. Chem. 25, 1157-1174
43. Jakalian, A., Jack, D. B., and Bayly, C. I. (2002) Fast, efficient generation of high-quality atomic charges. AM1-BCC model: II. Parameterization and validation. J. Comput. Chem. 23 1623-1641
44. Pandini, A., Fornili, A., Fraternali, F., and Kleinjung, J. (2012) Detection of allosteric signal transmission by information-Theoretic analysis of protein dynamics. FASEB J. 26, 868-881
45. Kabsch, W., and Sander, C. (1983) Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 22, 2577-2637
46. Barrett, C. P., Hall, B. A., and Noble, M. E. M. (2004) Dynamite: a simple way to gain insight into protein motions. Acta Crystallogr. D Biol. Crystallogr. 60, 2280-2287
47. Daura, X., Gademann, K., Jaun, B., Seebach, D., van Gunsteren, W. F., and Mark, A. E. (1999) Peptide folding: when simulation meets experiment. Angew. Chem. Int. Ed. 38, 236-240
48. Steinbrecher, T., Latzer, J., and Case, D. A. (2012) Revised AMBER parameters for bioorganic phosphates. J. Chem. Theory Comput. 8, 4405-4412
49. Choi, Y., Sims, G. E., Murphy, S., Miller, J. R., and Chan, A. P. (2012) Predicting the functional effect of amino acid substitutions and indels. PLoS One 7, e46688
50. Kumar, P., Henikoff, S., and Ng, P. C. (2009) Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat. Protoc. 4, 1073-1081
51. Adzhubei, I. A., Schmidt, S., Peshkin, L., Ramensky, V. E., Gerasimova, A., Bork, P., Kondrashov, A. S., and Sunyaev, S. R. (2010) A method and server for predicting damaging missense mutations. Nat. Methods 7, 248-249
52. Humphrey, W., Dalke, A., and Schulten, K. (1996) VMD: visual molecular dynamics. J. Mol. Graph. 14, 33-38
53. Notredame, C., Higgins, D. G., and Heringa, J. (2000) T-Coffee: a novel method for fast and accurate multiple sequence alignment. J. Mol. Biol. 302, 205-217
54. Azam, M., Seeliger, M. A., Gray, N. S., Kuriyan, J., and Daley, G. Q. (2008) Activation of tyrosine kinases by mutation of the gatekeeper threonine. Nat. Struct. Mol. Biol. 15, 1109-1118
55. Griswold, I. J., MacPartlin, M., Bumm, T., Goss, V. L., O'Hare, T., Lee, K. A., Corbin, A. S., Stoffregen, E. P., Smith, C., Johnson, K., Moseson, E. M., Wood, L. J., Polakiewicz, R. D., Druker, B. J., and Deininger, M. W. (2006) Kinase domain mutants of Bcr-Abl exhibit altered transformation potency, kinase activity, and substrate utilization, irrespective of sensitivity to imatinib. Mol. Cell. Biol. 26, 6082-6093
56. Shah, N. P. (2011) Ponatinib: targeting the T315I mutation in chronic myelogenous leukemia. Clin. Adv. Hematol. Oncol. 9, 925-926
57. Manley, P. W., Cowan-Jacob, S. W., Buchdunger, E., Fabbro, D., Fendrich, G., Furet, P., Meyer, T., and Zimmermann, J. (2002) Imatinib: a selective tyrosine kinase inhibitor. Eur. J. Cancer 38 (Suppl. 5), S19-S27
58. Bradeen, H. A., Eide, C. A., O'Hare, T., Johnson, K. J., Willis, S. G., Lee, F. Y., Druker, B. J., and Deininger, M. W. (2006) Comparison of imatinib mesylate, dasatinib (BMS-354825), and nilotinib (AMN107) in an N-ethyl-N-nitrosourea (ENU)-based mutagenesis screen: high efficacy of drug combinations. Blood 108, 2332-2338
59. Jabbour, E., and Kantarjian, H. (2012) Chronic myeloid leukemia: 2012 update on diagnosis, monitoring, and management. Am. J. Hematol. 87, 1037-1045
60. Baccarani, M., Cortes, J., Pane, F., Niederwieser, D., Saglio, G., Apperley, J., Cervantes, F., Deininger, M., Gratwohl, A., Guilhot, F., Hochhaus, A., Horowitz, M., Hughes, T., Kantarjian, H., Larson, R., Radich, J., Simonsson, B., Silver, R. T., Goldman, J., Hehlmann, R., and European, L. (2009) Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. J. Clin. Oncol. 27, 6041-6051
61. Zhou, T., Parillon, L., Li, F., Wang, Y., Keats, J., Lamore, S., Xu, Q., Shakespeare, W., Dalgarno, D., and Zhu, X. (2007) Crystal structure of the T315I mutant of AbI kinase. Chem. Biol. Drug. Des. 70, 171-181
62. Quintas-Cardama, A., and Cortes, J. (2008) Therapeutic options against BCR-ABL1 T315I-positive chronic myelogenous leukemia. Clin. Cancer Res. 14, 4392-4399
63. Wheeler, D. L., Dunn, E. F., and Harari, P. M. (2010) Understanding resistance to EGFR inhibitors-impact on future treatment strategies. Nat. Rev. Clin. Oncol. 7, 493-507
64. Guo, T., Agaram, N. P., Wong, G. C., Hom, G., D'Adamo, D., Maki, R. G., Schwartz, G. K., Veach, D., Clarkson, B. D., Singer, S., DeMatteo, R. P., Besmer, P., and Antonescu, C. R. (2007) Sorafenib inhibits the imatinib-resistant KITT670I gatekeeper mutation in gastrointestinal stromal tumor. Clin. Cancer Res. 13, 4874-4881
65. Barf, T., and Kaptein, A. (2012) Irreversible protein kinase inhibitors: balancing the benefits and risks. J. Med. Chem. 55, 6243-6262
66. Huang, W. S., Metcalf, C. A., Sundaramoorthi, R., Wang, Y., Zou, D., Thomas, R. M., Zhu, X., Cai, L., Wen, D., Liu, S., Romero, J., Qi, J., Chen, I., Banda, G., Lentini, S. P., Das, S., Xu, Q., Keats, J., Wang, F., Wardwell, S., Ning, Y., Snodgrass, J. T., Broudy, M. I., Russian, K., Zhou, T., Commodore, L., Narasimhan, N. I., Mohemmad, Q. K., Iuliucci, J., Rivera, V. M., Dalgarno, D. C., Sawyer, T. K., Clackson, T., and Shakespeare, W. C. (2010) Discovery of 3-[2-(imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1- yl)methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a potent, orally active pan-inhibitor of breakpoint cluster region-Abelson (BCR-ABL) kinase including the T315I gatekeeper mutant. J. Med. Chem. 53, 4701-4719
67. De Falco, V., Buonocore, P., Muthu, M., Torregrossa, L., Basolo, F., Billaud, M., Gozgit, J. M., Carlomagno, F., and Santoro, M. (2013) Ponatinib (AP24534) is a novel potent inhibitor of oncogenic RET mutants associated with thyroid cancer. J. Clin. Endocrinol. Metab. 98, E811-E819