Management of early stage chronic myeloid leukemia: State-of-the-art approach and future perspectives

Current Cancer Drug Targets

Volumn 13, Issue 7, 2013, Pages 749-754

  Galaverna, Federica ^a   Ghiggi, Chiara ^a   Guolo, Fabio ^a   Beltrami, Germana ^a   Dellepiane, Clara ^a   Giannoni, Livia ^a   Carella, Andrea ^a   Carella, Angelo M ^a  

^a UNIVERSITY OF GENOA   (Italy)

Author keywords

Chronic myeloid leukemia; New therapeutic strategies; Stem cell biology; Tyrosine kinase inhibitors

Indexed keywords

BCR ABL PROTEIN; BMS 215662; BOSUTINIB; CASPASE; CHLOROQUINE; CYTOCHROME C; DASATINIB; FINGOLIMOD; HYDROXYUREA; IMATINIB; INTERLEUKIN 1 RECEPTOR ACCESSORY PROTEIN; MACROLIDE; NILOTINIB; PHOSPHOPROTEIN PHOSPHATASE 2A; PONATINIB; PROTEIN BAX; PROTEIN FARNESYLTRANSFERASE INHIBITOR; PROTEIN TYROSINE KINASE INHIBITOR; REBASTINIB; SONIC HEDGEHOG PROTEIN; SONIDEGIB; TRANSCRIPTION FACTOR GLI1; TRANSCRIPTION FACTOR GLI2; UNCLASSIFIED DRUG;

ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALLOGENEIC STEM CELL TRANSPLANTATION; ARTICLE; AUTOPHAGY; CANCER STEM CELL; CD34 SELECTION; CELL VACUOLE; CHRONIC MYELOID LEUKEMIA; DIARRHEA; DRUG RESPONSE; DRUG TOLERABILITY; HUMAN; HYPERBILIRUBINEMIA; HYPERTRANSAMINASEMIA; LEUKEMIA RELAPSE; LIFE EXPECTANCY; LUNG DISEASE; MITOCHONDRION SWELLING; OVERALL SURVIVAL; PERIPHERAL OCCLUSIVE ARTERY DISEASE; PLEURA EFFUSION; POLYMERASE CHAIN REACTION; SIDE EFFECT; THROMBOCYTOPENIA; TRIACYLGLYCEROL LIPASE BLOOD LEVEL;

ANIMALS; ANTINEOPLASTIC AGENTS; DRUG DESIGN; DRUG RESISTANCE, NEOPLASM; HUMANS; LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE; MOLECULAR TARGETED THERAPY; NEOPLASM STAGING; NEOPLASTIC STEM CELLS; PROTEIN KINASE INHIBITORS; PROTEIN-TYROSINE KINASES; SIGNAL TRANSDUCTION;

EID: 84888051589     PISSN: 15680096     EISSN: 18735576     Source Type: Journal    
DOI: 10.2174/15680096113139990087     Document Type: Article

References (47)

1. Gambacorti-Passerini, C.; Antolini, L; Mahon, F. X.; Guilhot, F.; Deininger, M.; Fava, C.; Nagler, A.; Della Casa, C. M.; Morra, E.; Abruzzese, E.; D'Emilio, A.; Stagno, F.; Le Coutre, P; Hurtado-Monroy, R.; Santini, V.; Martino. B.; Pane, F.; Piccin, A.; Giraldo, P.; Assouline, S.; Durosinmi, M. A.; Leeksma, O.; Pogliani, E. M.; Puttini, M.; Jang, E.; Reiffers, J.; Valsecchi, M. G.; Kim, D. W. Multicenter independent assessment of outcomes in chronic myeloid leukemia patients treated with imatinib. J. Natl. Cancer Inst. 2011, 103 (7), 553-561.
2. Hehlmann, R.; Hochhaus, A.; Baccarani, M. European LeukemiaNet. Chronic myeloid leukaemia. Lancet 2007, 370 (9584), 342-350.
3. Druker, B. J.; Guilhot, F.; O'Brien, S. G.; Gathmann, I.; Kantarjian, H.; Gattermann, N.; Deininger, M. W.; 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, G.; Shepherd, J.; Saglio, G.; Gratwohl, A.; Nielsen, J. L.; Radich, J. P.; Simonsson, B.; Taylor, K.; Baccarani, M.; So, C.; Letvak, L.; Larson, R. A.; IRIS Investigators. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N. Engl. J. Med. 2006, 355 (23), 2408-2417.
4. Quintás-Cardama, A.; Cortes, J. Molecular biology of bcr-abl1-positive chronic myeloid leukemia. Blood 2009, 113 (8), 1619-1630.
5. Vardiman, J. W.; Melo, J. V.; Baccarani, M.; Thiele, J. Chronic myelogenous leukemia, BCR-ABL1 positive. In Swerdlowsh et al, Eds, WHO Classification of Tumours of Hematopoietic and Lymphoid Tissues, IARC, Lyon, 2008, pp. 32-37.
6. 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; European LeukemiaNet. Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. J. Clin. Oncol. 2009, 27 (35), 6041-6051.
7. Cortes, J. E.; Maru, A.; De Souza, C. A.; Guilhot, F.; Duville, L.; Powell, C.; Countouriotis, A.; Gambacorti-Passerini, C. Bosutinib versus Imatinib in newly diagnosed chronich phase chronic myeloid leukemia-BELA trial: 24-month follow-up. Blood 2011, 118 (21), 455.
8. 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.; Talpaz, M. Ponatinib in refractory Philadelphia chromosome-positive leukemias. N. Engl. J. Med. 2012, 367 (22), 2075-2088.
9. 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. M.; Kantarjian, H.; Taylor, K.; Verhoef, G.; Bolton, A. E.; Capdeville, R.; Druker, B. J.; IRIS Investigators Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N. Engl. J. Med. 2003, 348 (11), 994-1004.
10. 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.; International Randomised Study of Interferon versus STI571 (IRIS) Study Group. Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. N. Engl. J. Med. 2003, 349 (15), 1423-1432.
11. Hochhaus, A.; O'Brien, S. G.; Guilhot, F.; Druker, B. J.; Branford, S.; Foroni, L.; Goldman, J. M.; Müller, M. C.; Radich, J. P.; Rudoltz, M.; Mone, M.; Gathmann, I.; Hughes, T. P.; Larson, R. A.; IRIS Investigators. Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia 2009, 23 (6), 1054-1061.
12. Baccarani, M.; Rosti, G.; Castagnetti, F.; Haznedaroglu. I; Porkka, K.; Abruzzese, E.; Alimena, G.; Ehrencrona, H.; Hjorth-Hansen, H.; Kairisto, V.; Levato, L.; Martinelli, G.; Nagler, A.; Lanng Nielsen, J.; Ozbek, U.; Palandri, F.; Palmieri, F.; Pane, F.; Rege-Cambrin, G.; Russo, D.; Specchia, G.; Testoni, N.; Weiss-Bjerrum, O.; Saglio, G.; Simonsson, B. Comparison of imatinib 400 mg and 800 mg daily in the front-line treatment of high-risk, Philadelphiapositive chronic myeloid leukemia: a European LeukemiaNet Study. Blood 2009, 113 (19), 4497-4504.
13. Hehlmann, R.; Lauseker, M.; Jung-Munkwitz, S.; Leitner, A.; Müller, M. C.; Pletsch, N.; Proetel, U.; Haferlach, C.; Schlegelberger, B.; Balleisen, L.; Hänel, M.; Pfirrmann, M.; Krause, S. W.; Nerl, C.; Pralle, H.; Gratwohl, A.; Hossfeld, D. K.; Hasford, J.; Hochhaus, A.; Saussele, S. Tolerability-adapted imatinib 800 mg/d versus 400 mg/d versus 400 mg/d plus interferon-in newly diagnosed chronic myeloid leukemia. J. Clin. Oncol. 2011, 29 (12), 1634-1642.
14. Soverini, S.; Hochhaus, A.; Nicolini, F. E.; Gruber, F.; Lange, T.; Saglio, G.; Pane, F.; Müller, M. C.; Ernst, T.; Rosti, G.; Porkka, K.; Baccarani, M.; Cross, N. C.; Martinelli, G. BCR-ABL kinase domain mutation analysis in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: recommendations from an expert panel on behalf of European LeukemiaNet. Blood 2011, 118 (5), 1208-1215.
15. Kantarjian, H. M.; Giles, F. J.; Bhalla, K. N.; Pinilla-Ibarz, J.; Larson, R. A.; Gattermann, N.; Ottmann, O. G.; Hochhaus, A.; Radich, J. P.; Saglio, G.; Hughes, T. P.; Martinelli, G.; Kim, D. W.; Shou, Y.; Gallagher, N. J.; Blakesley, R.; Baccarani, M.; Cortes, J.; Le Coutre, P. D. Nilotinib is effective in patients with chronic myeloid leukemia in chronic phase after imatinib resistance or intolerance: 24-month follow-up results. Blood 2011, 117 (4), 1141-1145.
16. Hochhaus, A.; Kantarjian, H. M.; Baccarani, M.; Lipton, J. H.; Apperley, J. F.; Druker, B. J.; Facon, T.; Goldberg, S. L.; Cervantes, F.; Niederwieser, D.; Silver, R. T.; Stone, R. M.; Hughes, T. P.; Muller, M. C.; Ezzeddine, R.; Countouriotis, A. M.; Shah, N. P. Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy. Blood 2007, 109 (6), 2303-2309.
17. Rosti, G.; Palandri, F.; Castagnetti, F.; Breccia, M.; Levato, L.; Gugliotta, G.; Capucci, A.; Cedrone, M.; Fava, C.; Intermesoli, T.; Cambrin, G. R.; Stagno, F.; Tiribelli, M.; Amabile, M.; Luatti, S.; Poerio, A.; Soverini, S.; Testoni, N.; Martinelli, G.; Alimena, G.; Pane, F.; Saglio, G.; Baccarani, M.; GIMEMA CML Working Party. Nilotinib for the frontline treatment of Ph(+) chronic myeloid leukemia. Blood 2009, 114 (24), 4933-4938.
18. Saglio, G.; Kim, D. W.; Issaragrisil, S.; Le Coutre, P.; Etienne, G.; Lobo, C.; Pasquini, R.; Clark, R. E.; Hochhaus, A.; Hughes, T. P.; Gallagher, N.; Hoenekopp, A.; Dong, M.; Haque, A.; Larson, R. A.; Kantarjian, H. M.; ENESTnd Investigators. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N. Engl. J. Med. 2010, 362 (24), 2251-2259.
19. Kantarijan, H.; Hochhaus, A.; Saglio, G.; De Souza, C.; Flinn, I. W.; Stenke, L.; Goh, Y. T.; Rosti, G.; Nakamae, H.; Gallagher, N. J.; Hoenekopp, A.; Blakesley, R. E.; Larson, R. A.; Hughes, T. P. Nilotinib versus imatinib for the treatment of patients with newly diagnosed chronic phase, Philadelphia chromosome-positive, chronic myeloid leukaemia: 24-month minimum follow-up of the phase 3 randomised ENESTnd trial. Lancet Oncol. 2011, 12 (9), 841-851.
20. Kantarjian, H.; Shah, N. P.; Hochhaus, A.; Cortes, J.; Shah, S.; Ayala, M.; Moiraghi, B.; Shen, Z.; Mayer, J.; Pasquini, R.; Nakamae, H.; Huguet, F.; Boqué, C.; Chuah, C.; Bleickardt, E.; Bradley-Garelik, M. B.; Zhu, C.; Szatrowski, T.; Shapiro, D.; Baccarani, M. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N. Engl. J. Med. 2010, 362 (24), 2260-2270.
21. Kantarjian, H. M.; Shah, N. P.; Cortes, J. E.; Baccarani, M.; Agarwal, M. B.; Undurraga, M. S.; Wang, J.; Ipiña, J. J.; Kim, D. W.; Ogura, M.; Pavlovsky, C.; Junghanss, C.; Milone, J. H.; Nicolini, F. E.; Robak, T.; Van Droogenbroeck, J.; Vellenga, E.; Bradley-Garelik, M. B.; Zhu, C.; Hochhaus, A. Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION). Blood 2012, 119 (5), 1123-1129.
22. Marin, D. Initial choice of therapy among plenty for newly diagnosed chronic myeloid leukemia. Hematology Am. Soc. Hematol. Educ. Program. 2012, 2012, 115-121.
23. Graham, S. M.; Jørgensen, H. G.; Allan, E.; Pearson, C.; Alcorn, M. J.; Richmond, L.; Holyoake, T. L. Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to STI571 in vitro. Blood 2002, 99 (1), 319-325.
24. Copland, M; Hamilton, A.; Elrick, L. J.; Baird, J. W.; Allan, E. K.; Jordanides, N.; Barow, M.; Mountford, J. C.; Holyoake, T. L. Dasatinib (BMS-354825) targets an earlier progenitor population than imatinib in primary CML but does not eliminate the quiescent fraction. Blood 2006, 107 (11), 4532-4539.
25. Neviani, P.; Santhanam, R.; Trotta, R.; Notari, M.; Blaser, B. W.; Liu S.; Mao, H.; Chang, J. S.; Galietta, A.; Uttam, A.; Roy, D. C.; Valtieri, M.; Bruner-Klisovic, R.; Caligiuri, M. A.; Bloomfield, C. D.; Marcucci, G.; Perrotti, D. The tumor suppressor PP2A is functionally inactivated in blast crisis CML through the inhibitory activity of the BCR/ABL-regulated SET protein. Cancer Cell 2005, 8 (5), 355-368.
26. Walker, C.; Oaks, J. J.; Neviani, P.; Harb, J. G.; Santhanam, R.; Ma, Y.; Marcucci, G.; Van Brocklyn, J.; Chen, C. S.; Bittman, R.; Perrotti, D. PP2A Activating Drugs (PAD): Anti-leukemic and non-toxic activity of two novel and non-immunosuppressive FTY720 derivatives. Blood 2010, 116 (21), 2901.
27. Aktas, O.; Kury, P.; Kieseier, B.; Hartung, H. P. Fingolimod is a potential novel therapy for multiple sclerosis. Nat. Rev. Neurol. 2010, 6 (7), 373-382.
28. Neviani, P.; Santhanam, R.; Oaks, J. J.; Eiring, A. M.; Notari, M.; Blaser, B. W.; Liu, S.; Trotta, R.; Muthusamy, N.; Gambacorti-Passerini, C.; Druker, B. J.; Cortes, J.; Marcucci, G.; Chen, C. S.; Verrills, N. M.; Roy, D. C.; Caligiuri, M. A.; Bloomfield, C. D.; Byrd, J. C.; Perrotti, D. FTY720, a new alternative for treating blast crisis chronic myelogenous leukemia and Philadelphia chromosomepositive acute lymphocytic leukemia. J. Clin. Invest. 2007, 117 (9), 2408-2421.
29. Neviani, P.; Harb, J. G.; Oaks, J. J.; Walker, C.; Santhanam, R.; Paisie, C.; Ering, A.; Zhang, B.; Perazzona, B.; Mao, C.; Marcucci, G.; Holyoake, T. L.; Volinia, S.; Cortes, J. E.; Caligiuri, M. A.; Huettner, C.; Bittman, R.; Chen, C. S.; Arlinghaus, R. B.; Hokland, P.; Roy, D. C.; Bathia, R.; Perrotti, D. BCR-ABL1 kinase activity but not its expression is dispensable for Ph+ Quiescent stem cell survival which depends on the PP2A-controlled Jak2 activation and is sensitive to FTY720 treatment. Blood 2010, 116 (21), 515.
30. Oaks, J. J.; Mukhopadhyay, A.; Santhanam, R.; Saddoughi, S. A.; Walker, C.; Neviani, P.; Harb, J. G.; Ma, Y.; Verstovsek, S.; Marcucci, G.; Briesewitz, R.; Bittman, R.; Chen, C. S.; Quintas-Cardama, A.; Ogretmen, B.; Perrotti, D. Pharmacologic restoration of PP2A activity and interference with the SET-PP2A interplay by FTY720 and its non-immunosuppressive derivative as a novel and efficient therapy for Ph-negative myeloproliferative disorders. Blood 2010, 116 (21), 775.
31. Roberts, K. G.; Smith, A. M.; McDougall, F.; Carpenter, H.; Horan, M.; Neviani, P.; Powell, J. A.; Thomas, D.; Guthridge, M. A.; Perrotti, D.; Sim, A. T.; Ashman, L. K.; Verrills, N. M. Essential requirement for PP2A inhibition by the oncogenic receptor c-KIT suggests PP2A reactivation as a strategy to treat c-KIT+ cancers. Cancer Res. 2010, 70 (13), 5438-5447.
32. Corbin, A. S.; Agarwal, A.; Loriaux, M.; Cortes, J.; Deininger, M. W.; Druker, B. J. Human chronic myeloid leukemia stem cells are insensitive to imatinib despite inhibition of BCR-ABL activity. J. Clin. Invest. 2011, 121 (1), 396-409.
33. Samanta, A. K.; Chakraborty, S. N.; Wang, Y.; Kantarjian, H.; Sun, X.; Hood, J.; Perrotti, D.; Arlinghaus, R. B. Jak2 inhibition deactivates Lyn kinase through the SET-PP2A-SHP1 pathway, causing apoptosis in drug-resistant cells from chronic myelogenous leukemia patients. Oncogene 2009, 28 (14), 1669-1681.
34. Copland, M.; Pellicano, F.; Richmond, L.; Allan, E. K.; Hamilton, A.; Lee, F. Y.; Weinmann, R.; Holyoake, T. L. BMS-214662 potently induces apoptosis of chronic myeloid leukemia stem and progenitor cells and synergizes with tyrosine kinase inhibitors. Blood 2008, 111 (5), 2843-2853.
35. Bellodi, C.; Lidonnici, M. R; Hamilton, A.; Helgason, G. V.; Soliera, A. R.; Ronchetti, M.; Galavotti, S.; Young, K. W.; Selmi, T.; Yacobi, R.; Van Etten, R. A.; Donato, N.; Hunter, A.; Dinsdale, D.; Tirrò, E.; Vigneri, P.; Nicotera, P.; Dyer, M. J.; Holyoake, T.; Salomoni, P.; Calabretta, B. Targeting autophagy potentiates tyrosine kinase inhibitor-induced cell death in Philadelphia chromosome-positive cells, including primary CML stem cells. J. Clin. Invest. 2009, 119 (5), 1109-1123.
36. Kroemer, G.; Mariño, G.; Levine, B. Autophagy and the integrated stress response. Mol. Cell. 2010, 40 (2), 280-293.
37. Ertmer, A.; Huber, V.; Gilch, S.; Yoshimori, T.; Erfle, V.; Duyster, J.; Elsässer, H. P.; Schätzl, H. M. The anticancer drug imatinib induces cellular autophagy. Leukemia 2007, 21 (5), 936-942.
38. Altman, J. K.; Platanias, L. C. A new purpose for an old drug: inhibiting autophagy with clarithromycin. Leuk. Lymphoma 2012, 53 (7), 1255-1256.
39. Carella, A. M.; Beltrami, G.; Pica, G.; Carella, A.; Catania, G. Clarithromycin potentiates tyrosine kinase inhibitor treatment in patients with resistant chronic myeloid leukemia. Leuk. Lymphoma. 2012, 53 (7), 1409-1411.
40. Schafranek, L.; Leclercq, T. M.; White, D. L.; Hughes, T. P. Clarithromycin enhances dasatinib-induced cell death in CML cells, by inhibition of late stage autophagy. Leuk. Lymphoma. 2013, 54 (1), 198-201.
41. Zhao, C.; Chen, A.; Jamieson, C. H.; Fereshteh, M.; Abrahamsson, A.; Blum, J.; Kwon, H. Y.; Kim, J.; Chute, J. P.; Rizzieri, D.; Munchhof, M.; VanArsdale, T.; Beachy, P. A.; Reya, T. Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia. Nature 2009, 458 (7239), 776-779.
42. Dierks, C.; Beigi, R.; Guo, G. R.; Zirlik, K.; Stegert, M. R.; Manley, P.; Trussell, C.; Schmitt-Graeff, A.; Landwerlin, K.; Veelken, H.; Warmuth, M. Expansion of Bcr-Abl-positive leukemic stem cells is dependent on Hedgehog pathway activation. Cancer Cell. 2008, 14 (3), 238-249.
43. Irvine, D. A.; Heaney, N. B.; Holyoake, T. L. Optimising chronic myeloid leukaemia therapy in the face of resistance to tyrosine kinase inhibitors-A synthesis of clinical and laboratory data. Blood Rev. 2010, 24 (1), 1-9.
44. Jaras, M.; Johnels, P.; Hansen, N.; Agerstam, H.; Tsapogas, P.; Rissler, M.; Lassen, C.; Olofsson, T.; Bjerrum, O. W.; Richter, J.; Fioretos, T. Isolation and killing of candidate chronic myeloid leukemia stem cells by antibody targeting of IL-1 receptor accessory protein. Proc. Natl. Acad. Sci. U. S. A. 2010, 107 (37), 16280-16285.
45. rd.; 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.; Druker, B. J.; Clackson, T. AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell. 2009, 16 (5), 401-412.
46. 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.; Zhu, X. Structural mechanism of the Pan-BCRABL inhibitor ponatinib (AP24534): lessons for overcoming kinase inhibitor resistance. Chem. Biol. Drug Des. 2011, 77 (1), 1-11.
47. Mahon, F. X.; Rea, D.; Guilhot, J.; Guilhot, F.; Huguet, F.; Nicolini, F; Legros, L.; Charbonnier, A.; Guerci, A.; Varet, B.; Etienne, G.; Reiffers, J.; Rousselot, P. Intergroupe Français des Leucémies Myéloïdes Chroniques. Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicenter Stop Imatinib (STIM) trial. Lancet Oncol. 2010, 11 (11), 1029-1035.