Treatment options for chronic myeloid leukemia

Expert Opinion on Pharmacotherapy

Volumn 13, Issue 6, 2012, Pages 815-828

  Tanaka, Maria Florencia ^a   Kantarjian, Hagop ^b   Cortes, Jorge ^b   Ohanian, Maro ^b   Jabbour, Elias ^b  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

^b UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

Chronic Myeloid Leukemia; Dasatinib; Imatinib; Nilotinib; Treatment; Tyrosine kinase inhibitors

Indexed keywords

ALPHA INTERFERON; BOSUTINIB; CYTARABINE; DASATINIB; DCC 2036; HOMOHARRINGTONINE; IMATINIB; NILOTINIB; PEGINTERFERON ALPHA2A; PONATINIB; UNCLASSIFIED DRUG;

ALLOGENEIC STEM CELL TRANSPLANTATION; ALOPECIA; ANEMIA; ASTHENIA; CHRONIC MYELOID LEUKEMIA; DIARRHEA; DRUG EFFECT; DRUG EFFICACY; DRUG MEGADOSE; DRUG RESPONSE; DRUG TREATMENT FAILURE; DRUG WITHDRAWAL; EDEMA; FATIGUE; FEVER; FLUID RETENTION; HEADACHE; HEART ARRHYTHMIA; HUMAN; HYPERGLYCEMIA; MUSCLE CRAMP; MUSCLE SPASM; MUSCULOSKELETAL PAIN; MYALGIA; NAUSEA; NEUTROPENIA; PATIENT MONITORING; PERICARDIAL EFFUSION; PLEURA EFFUSION; PRACTICE GUIDELINE; PROGNOSIS; PRURITUS; RASH; RECOMMENDED DRUG DOSE; REVIEW; SIDE EFFECT; THROMBOCYTOPENIA; VOMITING;

FUSION PROTEINS, BCR-ABL; HUMANS; LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE; PROTEIN-TYROSINE KINASES; STEM CELL TRANSPLANTATION;

EID: 84863373152     PISSN: 14656566     EISSN: 17447666     Source Type: Journal    
DOI: 10.1517/14656566.2012.671296     Document Type: Review

References (102)

1. Jemal A, Siegel R, Xu J, et al. Cancer statistics, 2010. CA Cancer J Clin 2010;60:277-300
2. Faderl S, Talpaz M, Estrov Z, et al. The biology of chronic myeloid leukemia. N Engl J Med 1999;341:164-72
3. Rowley JD. Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 1973;243:290-3
4. Mandanas RA, Leibowitz DS, Gharehbaghi K, et al. Role of p21 RAS in p210 bcr-abl transformation of murine myeloid cells. Blood 1993;82:1838-47
5. Okuda K, Matulonis U, Salgia R, et al. Factor independence of human myeloid leukemia cell lines is associated with increased phosphorylation of the proto-oncogene Raf-1. Exp Hematol 1994;22:1111-17
6. Raitano AB, Halpern JR, Hambuch TM, et al. The Bcr-Abl leukemia oncogene activates Jun kinase and requires Jun for transformation. Proc Natl Acad Sci USA 1995;92:11746-50
7. Sawyers CL, Callahan W, Witte ON. Dominant negative MYC blocks transformation by ABL oncogenes. Cell 1992;70:901-10
8. Shuai K, Halpern J, ten Hoeve J, et al. Constitutive activation of STAT5 by the BCR-ABL oncogene in chronic myelogenous leukemia. Oncogene 1996;13:247-54
9. Silver RT, Woolf SH, Hehlmann R, et al. An evidence-based analysis of the effect of busulfan, hydroxyurea, interferon, and allogeneic bone marrow transplantation in treating the chronic phase of chronic myeloid leukemia: Developed for the American Society of Hematology. Blood 1999;94:1517-36
10. NCCN. NCCN Clinical Practice Guidelines in Oncology: Chronic myeloid leukemia. 2010. Available from: Hyyp://http://www.nccn.org/professionals/ physician gls/PDF/cml.pdf [Cited 20 September 2011]
11. Druker BJ, Lydon NB. Lessons learned from the development of an abl tyrosine kinase inhibitor for chronic myelogenous leukemia. J Clin Invest 2000;105:3-7
12. Druker BJ, Tamura S, Buchdunger E, et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med 1996;2:561-6
13. O'Brien SG, Guilhot F, Larson RA, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2003;348:994-1004
14. Deininger M, O'Brien SG, Guilhot F, et al. International randomized study of interferon vs. STI571 (IRIS) 8-year follow up: Sustained survival and low risk for progression of events in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatinib. Blood 2009;114, abstract 1126
15. Baccarani M, Rosti G, Castagnetti F, et al. Comparison of imatinib 400 mg and 800 mg daily in the front-line treatment of high-risk, Philadelphia- positive chronic myeloid leukemia: A European LeukemiaNet Study. Blood 2009;113:4497-504
16. Cortes JE, Baccarani M, Guilhot F, et al. Phase III, randomized, open-label study of daily imatinib mesylate 400 mg versus 800 mg in patients with newly diagnosed, previously untreated chronic myeloid leukemia in chronic phase using molecular end points: Tyrosine kinase inhibitor optimization and selectivity study. J Clin Oncol 2010;28:424-30
17. Preudhomme C, Guilhot J, Nicolini FE, et al. Imatinib plus peginterferon alfa-2a in chronic myeloid leukemia. N Engl J Med 2010;363:2511-21
18. Lombardo LJ, Lee FY, Chen P, et al. Discovery of N-(2-chloro-6- methylphenyl)- 2-(6-(4-(2-hydroxyethyl)- piperazin-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 2004;47:6658-61
19. Shah NP, Tran C, Lee FY, et al. Overriding imatinib resistance with a novel ABL kinase inhibitor. Science 2004;305:399-401
20. Kantarjian H, Shah NP, Hochhaus A, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2010;362:2260-70
21. Kantarjian HM, Shah NP, Cortes JE, et al. Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized phase III trial (DASISION). Blood 2012;119:1123-9
22. Weisberg E, Manley PW, Breitenstein W, et al. Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl. Cancer Cell 2005;7:129-41
23. O'Hare T, Walters DK, Stoffregen EP, et al. In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants. Cancer Res 2005;65:4500-5
24. Saglio G, Kim DW, Issaragrisil S, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med 2010;362:2251-9
25. Kantarjian HM, Hochhaus A, Saglio G, et al. 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 III randomised ENESTnd trial. Lancet Oncol 2011;12:841-51
26. Kantarjian H, Giles F, Wunderle L, et al. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive all. N Engl J Med 2006;354:2542-51
27. Gambacorti-Passerini C, Kantarjian H, Kim DW, et al. An ongoing phase 3 study of bosutinib (SKI-606) versus imatinib in patients with newly diagnosed chronic phase chronic myeloid leukemia. Blood 2010; 116: Abstract 208
28. Hughes TP, Kaeda J, Branford S, et al. Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. N Engl J Med 2003;349:1423-32
29. Jabbour E, Kantarjian H, O'Brien S, et al. The achievement of an early complete cytogenetic response is a major determinant for outcome in patients with early chronic phase chronic myeloid leukemia treated with tyrosine kinase inhibitors. Blood 2011;118(17):4541-6
30. Hehlmann R, Lauseker M, Jung-Munkwitz S, et al. Tolerability-adapted imatinib 800 mg/d versus 400 mg/d versus 400 mg/d plus interferon-alpha in newly diagnosed chronic myeloid leukemia. J Clin Oncol 2011;29:1634-42
31. Baccarani M, Cortes J, Pane F, et al. Chronic myeloid leukemia: An update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol 2009;27:6041-51
32. Marin D, Milojkovic D, Olavarria E, et al. European LeukemiaNet criteria for failure or suboptimal response reliably identify patients with CML in early chronic phase treated with imatinib whose eventual outcome is poor. Blood 2008;112:4437-44
33. Alvarado Y, Kantarjian H, O'Brien S, et al. Significance of suboptimal response to imatinib, as defined by the European LeukemiaNet, in the long-term outcome of patients with early chronic myeloid leukemia in chronic phase. Cancer 2009;115:3709-18
34. Kantarjian HM, Talpaz M, O'Brien S, et al. Survival benefit with imatinib mesylate versus interferon-alpha-based regimens in newly diagnosed chronic-phase chronic myelogenous leukemia. Blood 2006;108:1835-40
35. Roy L, Guilhot J, Krahnke T, et al. Survival advantage from imatinib compared with the combination interferon-alpha plus cytarabine in chronic-phase chronic myelogenous leukemia: Historical comparison between two phase III trials. Blood 2006;108:1478-84
36. Jabbour E, Kantarjian HM, O'Brien S, et al. Front-line therapy with second-generation tyrosine kinase inhibitors in patients with early chronic phase chronic myeloid leukemia: What is the optimal response? J Clin Oncol 2011;29(32):4260-5
37. Hochhaus A, O'Brien SG, Guilhot F, et al. Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia 2009;23:1054-61
38. Bixby D, Talpaz M. Mechanisms of resistance to tyrosine kinase inhibitors in chronic myeloid leukemia and recent therapeutic strategies to overcome resistance. Hematology Am Soc Hematol Educ Program 2009;461-76
39. Hochhaus A, Kreil S, Corbin AS, et al. Molecular and chromosomal mechanisms of resistance to imatinib (STI571) therapy. Leukemia 2002;16:2190-6
40. Lee F, Fandi A, Voi M. Overcoming kinase resistance in chronic myeloid leukemia. Int J Biochem Cell Biol 2008;40:334-43
41. Nicolini FE, Corm S, Le QH, et al. Mutation status and clinical outcome of 89 imatinib mesylate-resistant chronic myelogenous leukemia patients: A retrospective analysis from the French intergroup of CML (Fi(phi)-LMC GROUP). Leukemia 2006;20:1061-6
42. Jabbour E, Kantarjian H, Jones D, et al. Frequency and clinical significance of BCR-ABL mutations in patients with chronic myeloid leukemia treated with imatinib mesylate. Leukemia 2006;20:1767-73
43. Khorashad JS, de Lavallade H, Apperley JF, et al. Finding of kinase domain mutations in patients with chronic phase chronic myeloid leukemia responding to imatinib may identify those at high risk of disease progression. J Clin Oncol 2008;26:4806-13
44. Weisberg E, Griffin JD. Mechanism of resistance to the ABL tyrosine kinase inhibitor STI571 in BCR/ABLtransformed hematopoietic cell lines. Blood 2000;95:3498-505
45. Mahon FX, Deininger MW, Schultheis B, et al. Selection and characterization of BCR-ABL positive cell lines with differential sensitivity to the tyrosine kinase inhibitor STI571: Diverse mechanisms of resistance. Blood 2000;96:1070-9
46. Che XF, Nakajima Y, Sumizawa T, et al. Reversal of P-glycoprotein mediated multidrug resistance by a newly synthesized 1,4-benzothiazipine derivative, JTV-519. Cancer Lett 2002;187:111-19
47. Gambacorti-Passerini C, Barni R, le Coutre P, et al. Role of alpha1 acid glycoprotein in the in vivo resistance of human BCR-ABL(+) leukemic cells to the abl inhibitor STI571. J Natl Cancer Inst 2000;92:1641-50
48. Zhang WW, Cortes JE, Yao H, et al. Predictors of primary imatinib resistance in chronic myelogenous leukemia are distinct from those in secondary imatinib resistance. J Clin Oncol 2009;27:3642-9
49. Redaelli S, Piazza R, Rostagno R, et al. Activity of bosutinib, dasatinib, and nilotinib against 18 imatinib-resistant BCR/ABL mutants. J Clin Oncol 2009;27:469-71
50. Muller MC, Cortes JE, Kim DW, et al. Dasatinib treatment of chronic-phase chronic myeloid leukemia: Analysis of responses according to preexisting BCR-ABL mutations. Blood 2009;114:4944-53
51. Hughes T, Saglio G, Branford S, et al. Impact of baseline BCR-ABL mutations on response to nilotinib in patients with chronic myeloid leukemia in chronic phase. J Clin Oncol 2009;27:4204-10
52. Marin D, Bazeos A, Mahon FX, et al. Adherence is the critical factor for achieving molecular responses in patients with chronic myeloid leukemia who achieve complete cytogenetic responses on imatinib. J Clin Oncol 2010;28:2381-8
53. Darkow T, Henk HJ, Thomas SK, et al. Treatment interruptions and non-adherence with imatinib and associated healthcare costs: A retrospective analysis among managed care patients with chronic myelogenous leukaemia. Pharmacoeconomics 2007;25:481-96
54. Noens L, van Lierde MA, De Bock R, et al. Prevalence, determinants, and outcomes of nonadherence to imatinib therapy in patients with chronic myeloid leukemia: The ADAGIO study. Blood 2009;113:5401-11
55. Jabbour E, Kantarjian HM, Jones D, et al. Imatinib mesylate dose escalation is associated with durable responses in patients with chronic myeloid leukemia after cytogenetic failure on standard-dose imatinib therapy. Blood 2009;113:2154-60
56. Mauro MJ BF, Cervantes JH, et al. Dasatinib 2-year efficacy in patients with chronic-phase chronic myeloid leukemia with resistance or intolerance to Imatinib (START-C) ASCO Annual Meeting Abstracts. J Clin Oncol 2009;26:abstract 7009
57. Brave M, Goodman V, Kaminskas E, et al. Sprycel for chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia resistant to or intolerant of imatinib mesylate. Clin Cancer Res 2008;14:352-9
58. Shah NP, Kantarjian HM, Kim DW, et al. Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemia. J Clin Oncol 2008;26:3204-12
59. Porkka K, Khoury HJ, Paquette RL, et al. Dasatinib 100 mg once daily minimizes the occurrence of pleural effusion in patients with chronic myeloid leukemia in chronic phase and efficacy is unaffected in patients who develop pleural effusion. Cancer 2010;116:377-86
60. Nicolini FE, Mauro MJ, Martinelli G, et al. Epidemiologic study on survival of chronic myeloid leukemia and Ph(+) acute lymphoblastic leukemia patients with BCR-ABL T315I mutation. Blood 2009;114:5271-8
61. Giles FJ, Abruzzese E, Rosti G, et al. Nilotinib is active in chronic and accelerated phase chronic myeloid leukemia following failure of imatinib and dasatinib therapy. Leukemia 2010;24:1299-301
62. Laneuville P, Dilea C, Yin OQ, et al. Comparative In vitro cellular data alone are insufficient to predict clinical responses and guide the choice of BCR-ABL inhibitor for treating imatinib-resistant chronic myeloid leukemia. J Clin Oncol 2010;28:e169-71; author reply e72
63. Willis SG, Lange T, Demehri S, et al. High-sensitivity detection of BCR-ABL kinase domain mutations in imatinib-naive patients: Correlation with clonal cytogenetic evolution but not response to therapy. Blood 2005;106:2128-37
64. Hasford J, Baccarani M, Hoffmann V, et al. Predicting complete cytogenetic response and subsequent progression-free survival in 2060 patients with CML on imatinib treatment: The EUTOS score. Blood 2011;118:686-92
65. Marin D, Ibrahim AR, Lucas C, et al. Assessment of BCR-ABL1 Transcript Levels at 3 Months Is the Only Requirement for Predicting Outcome for Patients With Chronic Myeloid Leukemia Treated With Tyrosine Kinase Inhibitors. J Clin Oncol 2012;30:232-8
66. Cortes J, Jabbour E, Kantarjian H, et al. Dynamics of BCR-ABL kinase domain mutations in chronic myeloid leukemia after sequential treatment with multiple tyrosine kinase inhibitors. Blood 2007;110:4005-11
67. Jabbour E, Kantarjian H, Jones D, et al. Characteristics and outcomes of patients with chronic myeloid leukemia and T315I mutation following failure of imatinib mesylate therapy. Blood 2008;112:53-5
68. Jabbour E, Jones D, Kantarjian HM, et al. 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 2009;114:2037-43
69. Jabbour E, Kantarjian H, O'Brien S, et al. Predictive factors for outcome and response in patients treated with second-generation tyrosine kinase inhibitors for chronic myeloid leukemia in chronic phase after imatinib failure. Blood 2011;117:1822-7
70. Mahon FX, Rea D, Guilhot J, et al. Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: The prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol 2010;11:1029-35
71. Jabbour E, Kantarjian HM, Abruzzo LV, et al. Chromosomal abnormalities in Philadelphia chromosome negative metaphases appearing during imatinib mesylate therapy in patients with newly diagnosed chronic myeloid leukemia in chronic phase. Blood 2007;110:2991-5
72. Soverini S, Colarossi S, Gnani A, et al. Contribution of ABL kinase domain mutations to imatinib resistance in different subsets of Philadelphia-positive patients: By the GIMEMA Working Party on Chronic Myeloid Leukemia. Clin Cancer Res 2006;12:7374-9
73. Apperley JF, Cortes JE, Kim DW, et al. Dasatinib in the treatment of chronic myeloid leukemia in accelerated phase after imatinib failure: The START a trial. J Clin Oncol 2009;27:3472-9
74. le Coutre PD, Giles FJ, Hochhaus A, et al. Nilotinib in patients with Ph+ chronic myeloid leukemia in accelerated phase following imatinib resistance or intolerance: 24-month follow-up results. Leukemia 2011; 11 Nocember 2011 [Epub ahead of print]; doi: 10.1038/leu.2011.323
75. Gambacorti-Passerini C KH, Baccarani M, et al. Bosutinib demonstrates clinical activity and is well-tolerated among patients with AP and BP CML and Ph ALL. J Clin Oncol 2008;26:abstract 7049
76. Sawyers CL, Hochhaus A, Feldman E, et al. Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: Results of a phase II study. Blood 2002;99:3530-9
77. Druker BJ, Sawyers CL, Kantarjian H, et al. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med 2001;344:1038-42
78. Kantarjian HM, Cortes J, O'Brien S, et al. Imatinib mesylate (STI571) therapy for Philadelphia chromosome-positive chronic myelogenous leukemia in blast phase. Blood 2002;99:3547-53
79. Thiesing JT, Ohno-Jones S, Kolibaba KS, et al. Efficacy of STI571, an abl tyrosine kinase inhibitor, in conjunction with other antileukemic agents against bcr-abl-positive cells. Blood 2000;96:3195-9
80. La Rosee P, O'Dwyer ME, Druker BJ. Insights from pre-clinical studies for new combination treatment regimens with the Bcr-Abl kinase inhibitor imatinib mesylate (Gleevec/Glivec) in chronic myelogenous leukemia: A translational perspective. Leukemia 2002;16:1213-19
81. Deau B, Nicolini FE, Guilhot J, et al. The addition of daunorubicin to imatinib mesylate in combination with cytarabine improves the response rate and the survival of patients with myeloid blast crisis chronic myelogenous leukemia (AFR01 study). Leuk Res 2011;35:777-82
82. de Labarthe A, Rousselot P, Huguet-Rigal F, et al. Imatinib combined with induction or consolidation chemotherapy in patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia: Results of the GRAAPH-2003 study. Blood 2007;109:1408-13
83. Yanada M, Naoe T. Imatinib combined chemotherapy for Philadelphia chromosome-positive acute lymphoblastic leukemia: Major challenges in current practice. Leuk Lymphoma 2006;47:1747-53
84. Thomas DA, Faderl S, Cortes J, et al. Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood 2004;103:4396-407
85. Ravandi F, O'Brien S, Thomas D, et al. First report of phase II study of dasatinib with hyper-CVAD for the frontline treatment of patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia. Blood 2010;116:2070-7
86. Talpaz M, Shah NP, Kantarjian H, et al. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med 2006;354:2531-41
87. Cortes J, Rousselot P, Kim DW, et al. Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis. Blood 2007;109:3207-13
88. Quintas-Cardama A, Kantarjian H, Garcia-Manero G, et al. A pilot study of imatinib, low-dose cytarabine and idarubicin for patients with chronic myeloid leukemia in myeloid blast phase. Leuk Lymphoma 2007;48:283-9
89. Oki Y, Kantarjian HM, Gharibyan V, et al. Phase II study of low-dose decitabine in combination with imatinib mesylate in patients with accelerated or myeloid blastic phase of chronic myelogenous leukemia. Cancer 2007;109:899-906
90. Oehler VG, Gooley T, Snyder DS, et al. The effects of imatinib mesylate treatment before allogeneic transplantation for chronic myeloid leukemia. Blood 2007;109:1782-9
91. Carpenter PA, Snyder DS, Flowers ME, et al. Prophylactic administration of imatinib after hematopoietic cell transplantation for high-risk Philadelphia chromosome-positive leukemia. Blood 2007;109:2791-3
92. Olavarria E, Siddique S, Griffiths MJ, et al. Posttransplantation imatinib as a strategy to postpone the requirement for immunotherapy in patients undergoing reduced-intensity allografts for chronic myeloid leukemia. Blood 2007;110:4614-17
93. Pye SM, Cortes J, Ault P, et al. The effects of imatinib on pregnancy outcome. Blood 2008;111:5505-8
94. Ali R, Ozkalemkas F, Ozkocaman V, et al. Successful pregnancy and delivery in a patient with chronic myelogenous leukemia (CML), and management of CML with leukapheresis during pregnancy: A case report and review of the literature. Jpn J Clin Oncol 2004;34:215-17
95. Martinelli P, Martinelli V, Agangi A, et al. Interferon alfa treatment for pregnant women affected by essential thrombocythemia: Case reports and a review. Am J Obstet Gynecol 2004;191:2016-20
96. O'Hare T, Shakespeare WC, Zhu X, et al. AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell 2009;16:401-12
97. Cortes J, Talpaz M, Bixby D, et al. A Phase I trial of oral ponatinib (AP24534) in patients with refractory Chronic Myelogenous Leukemia (CML) and other hematologic malignancies: Emerging safety and clinical response findings. Blood 2010;116:absctract 210
98. Gontarewicz A, Balabanov S, Keller G, et al. Simultaneous targeting of Aurora kinases and Bcr-Abl kinase by the small molecule inhibitor PHA-739358 is effective against imatinib-resistant BCRABL mutations including T315I. Blood 2008;111:4355-64
99. Chan WW, Wise SC, Kaufman MD, et al. Conformational control inhibition of the BCR-ABL1 tyrosine kinase, including the gatekeeper T315I mutant, by the switch-control inhibitor DCC-2036. Cancer Cell 2011;19:556-68
100. Quintas-Cardama A, Kantarjian H, Cortes J. Homoharringtonine, omacetaxine mepesuccinate, and chronic myeloid leukemia circa 2009. Cancer 2009;115:5382-93
101. Cortes J RD, Parikh P, et al. Safety and efficacy of subcutaneous- administered omacetaxine mepesuccinate in Chronic Myeloid Leukemia (CML) patients who are resistant or intolerant to two or more tyrosine kinase inhibitors - results of a multicenter Phase II/III Study. Blood 2009;114:abstract 861
102. Bin Zhang DI, Ho YW, Buonamici S, et al. Inhibition of Chronic myeloid leukemia stem cells by the combination of the hedgehog pathway inhibitor LDE225 with nilotinib. Blood 2010;116:abstract 514