Mechanisms of resistance to imatinib and second-generation tyrosine inhibitors in chronic myeloid leukemia

Clinical Cancer Research

Volumn 15, Issue 24, 2009, Pages 7519-7527

  Milojkovic, Dragana ^a   Apperley, Jane F ^b  

^a HAMMERSMITH HOSPITAL   (United Kingdom)

^b IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ABELSON KINASE; BCR ABL PROTEIN; CELL ENZYME; CYTOCHROME P450 3A4; DASATINIB; IMATINIB; ISOENZYME; NILOTINIB; ORGANIC CATION TRANSPORTER 1; PROTEIN TYROSINE KINASE INHIBITOR;

BIOAVAILABILITY; CANCER RESISTANCE; CHRONIC MYELOID LEUKEMIA; DRUG METABOLISM; GENOTYPE; HUMAN; IN VITRO STUDY; NONHUMAN; PATIENT COMPLIANCE; PLASMA PROTEIN BINDING; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; STEM CELL; WILD TYPE;

EID: 73349097214     PISSN: 10780432     EISSN: None     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-09-1068     Document Type: Review

References (100)

1. Hantschel O, Superti-Furga G. Regulation of the c-Abl and Bcr-Abl tyrosine kinases. Nat Rev Mol Cell Biol 2004;5:33-44.
2. Milojkovic D, Apperley J. State-of-the-art in the treatment of chronic myeloid leukaemia. Curr Opin Oncol 2008;20:112-21.
3. Melo J. Inviting leukemic cells to waltz with the devil. Nat Med 2001;7:156-7.
4. Quintas-Cardama A, Cortes J. Molecular biology of bcr-abl1-positive chronic myeloid leukemia. Blood 2009;113:1619-30.
5. Druker BJ, Talpaz M, Resta DJ, et al. Efficacy and safety of a specific inhibitor of the BCRABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 2001;344:1031-7.
6. Deininger M, Buchdunger E, Druker BJ. The development of imatinib as a therapeutic agent for chronic myeloid leukemia. Blood 2005;105: 2640-53.
7. Hochhaus A, O'Brien SG, Guilhot F, et al. Sixyear follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia 2009;23:1054-61.
8. Baccarani M, Saglio G, Goldman J, et al. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood 2006;108:1809-20.
9. Hughes T, Deininger M, Hochhaus A, et al. 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 2006;108:28-37.
10. Marin D, Kaeda J, Szydlo R, et al. Monitoring patients in complete cytogenetic remission after treatment of CML in chronic phase with imatinib: patterns of residual leukaemia and prognostic factors for cytogenetic relapse. Leukemia 2005; 19:507-12.
11. 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.
12. 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.
13. Press RD, Galderisi C, Yang R, et al. A half-log increase in BCR-ABL RNA predicts a higher risk of relapse in patients with chronic myeloid leukemia with an imatinib-induced complete cytogenetic response. Clin Cancer Res 2007;13:6136-43.
14. Shah NP, Tran C, Lee FY, Chen P, Norris D, Sawyers CL. Overriding imatinib resistance with a novel ABL kinase inhibitor. Science 2004;305: 399-401.
15. 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.
16. 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.
17. Larson RA, Druker BJ, Guilhot F, et al. Imatinib pharmacokinetics and its correlation with response and safety in chronic-phase chronic myeloid leukemia: a subanalysis of the IRIS study. Blood 2008;111:4022-8.
18. Li X, He Y, Ruiz CH, Koenig M, Cameron MD. Characterization of dasatinib and its structural analogs as CYP3A4 mechanism-based inactivators and the proposed bioactivation pathways. Drug Metab Dispos 2009;37:1242-50.
19. Deremer DL, Ustun C, Natarajan K. Nilotinib: a second-generation tyrosine kinase inhibitor for the treatment of chronic myelogenous leukemia. Clin Ther 2008;30:1956-75.
20. 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.
21. Jorgensen HG, Elliott MA, Allan EK, Carr CE, Holyoake TL, Smith KD. Alpha1-acid glycoprotein expressed in the plasma of chronic myeloid leukemia patients does not mediate significant in vitro resistance to STI571. Blood 2002;99: 713-5.
22. Smith KD, Paterson S. Binding of alpha-1-acid glycoprotein to imatinib following increased dosage of drug. Haematologica 2005;90 Suppl: ELT01.
23. Christopher LJ, Cui D, Wu C, et al. Metabolism and disposition of dasatinib after oral administration to humans. Drug Metab Dispos 2008;36: 1357-64.
24. Arceci RJ. Clinical significance of P-glycoprotein in multidrug resistance malignancies. Blood 1993;81:2215-22.
25. Lagas JS, van Waterschoot RA, van Tilburg VA, et al. Brain accumulation of dasatinib is restricted by P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) and can be enhanced by elacridar treatment. Clin Cancer Res 2009;2344-51.
26. Doyle LA, Ross DD. Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2). Oncogene 2003;22:7340-58.
27. Kuwazuru Y, Yoshimura A, Hanada S, et al. Expression of the multidrug transporter, P-glycoprotein, in chronic myelogenous leukaemia cells in blast crisis. Br J Haematol 1990;74:24-9.
28. Mahon FX, Belloc F, Lagarde V, et al. MDR1 gene overexpression confers resistance to imatinib mesylate in leukemia cell line models. Blood 2003;101:2368-73.
29. Ferrao PT, Frost MJ, Siah SP, Ashman LK. Overexpression of P-glycoprotein in K562 cells does not confer resistance to the growth inhibitory effects of imatinib (STI571) in vitro. Blood 2003;102:4499-503.
30. Assef Y, Rubio F, Colo G, del Monaco S, Costas MA, Kotsias BA. Imatinib resistance in multidrug-resistant K562 human leukemic cells. Leuk Res 2009;33:710-6.
31. Galimberti S, Cervetti G, Guerrini F, et al. Quantitative molecularmonitoring of BCR-ABL and MDR1 transcripts in patients with chronic myeloid leukemia during Imatinib treatment. Cancer Genet Cytogenet 2005;162:57-62.
32. Hatziieremia S, Jordanides NE, Holyoake TL, Mountford JC, Jorgensen HG. Inhibition of MDR1 does not sensitize primitive chronic myeloid leukemia CD34+ cells to imatinib. Exp Hematol 2009;37:692-700.
33. Jordanides NE, Jorgensen HG, Holyoake TL, Mountford JC. Functional ABCG2 is overexpressed on primary CML CD34+ cells and is inhibited by imatinib mesylate. Blood 2006;15: 1370-3.
34. Mahon FX, Hayette S, Lagarde V, et al. Evidence that resistance to nilotinib may be due to BCR-ABL, Pgp, or Src kinase overexpression. Cancer Res 2008;68:9809-16.
35. Brendel C, Scharenberg C, Dohse M, et al. Imatinib mesylate and nilotinib (AMN107) exhibit high-affinity interact ion with ABCG2 on primitive hematopoietic stem cells. Leukemia 2007;21:1267-75.
36. Tiwari AK, Sodani K, Wang SR, et al. Nilotinib (AMN107, Tasigna) reverses multidrug resistance by inhibiting the activity of the ABCB1/ Pgp and ABCG2/BCRP/MXR transporters. Biochem Pharmacol 2009;78:153-61.
37. Hiwase DK, Saunders V, Hewett D, et al. Dasatinib cellular uptake and efflux in chronic myeloid leukemia cells: therapeutic implications. Clin Cancer Res 2008;14:3881-8.
38. Chen Y, Agarwal S, Shaik NM, Chen C, Yang Z, Elmquist WF. P-glycoprotein and breast cancer resistance protein influence brain distribution of dasatinib. Journal Pharmacol Exp Ther 2009; 330:956-63.
39. Kamath AV, Wang J, Lee FY, Marathe PH. Preclinical pharmacokinetics and in vitro metabolism of dasatinib (BMS-354825): a potent oral multi-targeted kinase inhibitor against SRC and BCR-ABL. Cancer Chemother Pharmacol 2008;61:365-76.
40. Thomas J, Wang L, Clark RE, Pirmohamed M. Active transport of imatinib into and out of cells: implications for drug resistance. Blood 2004;104: 3739-45.
41. Crossman LC, Druker BJ, Deininger MW, Pirmohamed M, Wang L, Clark RE. hOCT 1 and resistance to imatinib. Blood 2005;106:1133-4, author reply 4.
42. Sakata T, Anzai N, Shin HJ, et al. Novel single nucleotide polymorphisms of organic cation transporter 1 (SLC22A1) affecting transport functions. Biochem Biophys Res Commun 2004;313:789-93.
43. Hu S, Franke RM, Filipski KK, et al. Interaction of imatinib with human organic ion carriers. Clin Cancer Res 2008;14:3141-8.
44. White DL, Saunders VA, Dang P, et al. Most CML patients who have a suboptimal response to imatinib have low OCT-1 activity: higher doses of imatinib may overcome the negative impact of low OCT-1 activity. Blood 2007;110: 4064-72.
45. White DL, Dang P, Frede A, et al. CML patients with low OCT-1 activity achieve better molecular responses on high dose imatinib than on standard dose. those with high OCT-1 activity have excellent responses on either dose: a TOPS correlative study. Blood 2008;112:3187a.
46. White DL, Saunders VA, Dang P, et al. 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 2006;108:697-704.
47. Dulucq S, Bouchet S, Turcq B, et al. Multidrug resistance gene (MDR1) polymorphisms are associated with major molecular responses to standard-dose imatinib in chronic myeloid leukemia. Blood 2008;112:2024-7.
48. Kim DH, Sriharsha L, Xu W, et al. Clinical relevance of a pharmacogenetic approach using multiple candidate genes to predict response and resistance to imatinib therapy in chronic myeloid leukemia. Clin Cancer Res 2009;15: 4750-8.
49. Majlis A, Smith TL, Talpaz M, O'Brien S, Rios MB, Kantarjian HM. Significance of cytogenetic clonal evolution in chronic myelogenous leukemia. J Clin Oncol 1996;14:196-203.
50. Johansson B, Fioretos T, Mitelman F. Cytogenetic and molecular genetic evolution of chronic myeloid leukemia. Acta Haematol 2002;107:76-94.
51. O'Dwyer ME, Mauro MJ, Blasdel C, et al. Clonal evolution and lack of cytogenetic response are adverse prognostic factors for hematologic relapse of chronic phase CML patients treated with imatinib mesylate. Blood 2004;103:451-5.
52. Cortes JE, Talpaz M, Giles F, et al. Prognostic significance of cytogenetic clonal evolution in patients with chronic myelogenous leukemia on imatinib mesylate therapy. Blood 2003;101: 3794-800.
53. Cortes J, O'Dwyer ME. Clonal evolution in chronic myelogenous leukemia. Hematol Oncol Clin North Am 2004;18:671-84 [x.].
54. Lahaye T, Riehm B, Berger U, et al. Response and resistance in 300 patients with BCR-ABLpositive leukemias treated with imatinib in a single center: a 4.5-year follow-up. Cancer 2005; 103:1659-69.
55. 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.
56. Geahlen RL, Handley MD, Harrison ML. Molecular interdiction of Src-family kinase signaling in hematopoietic cells. Oncogene 2004;23:8024-32.
57. Danhauser-Riedl S, Warmuth M, Druker BJ, Emmerich B, Hallek M. Activation of Src kinases p53/56lyn and p59hck by p210bcr/abl in myeloid cells. Cancer Res 1996;56:3589-96.
58. Donato NJ, Wu JY, Stapley J, et al. BCR-ABL independence and LYN kinase overexpression in chronic myelogenous leukemia cells selected for resistance to STI571. Blood 2003;101:690-8.
59. Hu Y, Swerdlow S, Duffy TM, Weinmann R, Lee FY, Li S. Targeting multiple kinase pathways in leukemic progenitors and stem cells is essential for improved treatment of Ph+ leukemia in mice. Proc Natl Acad Sci U S A 2006; 103:16870-5.
60. Dai Y, Rahmani M, Corey SJ, Dent P, Grant SA. Bcr/Abl-independent, Lyn-dependent form of imatinib mesylate (STI-571) resistance is associated with altered expression of Bcl-2. J Biol Chem 2004;279:34227-39.
61. Schindler T, Bornmann W, Pellicena P, Miller WT, Clarkson B, Kuriyan J. Structural mechanism for STI-571 inhibition of abelson tyrosine kinase. Science 2000;289:1938-42.
62. O'Hare T, Eide CA, Deininger MW. Persistent LYN signaling in imatinib-resistant, BCR-ABLindependent chronic myelogenous leukemia. J Natl Cancer Inst 2008;100:908-9.
63. Copland M, Hamilton A, Elrick LJ, et al. Dasatinib (BMS-354825) targets an earlier progenitor population than imatinib in primary CML but does not eliminate the quiescent fraction. Blood 2006;107:4532-9.
64. Jiang X, Zhao Y, Smith C, et al. Chronic myeloid leukemia stem cells possess multiple unique features of resistance to BCR-ABL targeted therapies. Leukemia 2007;21:926-35.
65. Jin L, Tabe Y, Konoplev S, et al. CXCR4 upregulation by imatinib induces chronic myelogenous leukemia (CML) cell migration to bone marrow stroma and promotes survival of quiescent CML cells. Mol Cancer Ther 2008;7:48-58.
66. Konig H, Copland M, Chu S, Jove R, Holyoake TL, Bhatia R. Effects of dasatinib on SRC kinase activity and downstream intracellular signaling in primitive chronic myelogenous leukemia hematopoietic cells. Cancer Res 2008;68: 9624-33.
67. Jorgensen HG, Allan EK, Jordanides NE, Mountford JC, Holyoake TL. Nilotinib exerts equipotent antiproliferative effects to imatinib and does not induce apoptosis in CD34+ CML cells. Blood 2007;109:4016-9.
68. Copland M, Pellicano F, Richmond L, et al. BMS-214662 potently induces apoptosis of chronic myeloid leukemia stem and progenitor cells and synergizes with tyrosine kinase inhibitors. Blood 2008;111:2843-53.
69. Holtz M, Forman SJ, Bhatia R. Growth factor stimulation reduces residual quiescent chronic myelogenous leukemia progenitors remaining after imatinib treatment. Cancer Res 2007;67: 1113-20.
70. Copland M, Fraser AR, Harrison SJ, Holyoake TL. Targeting the silent minority: emerging immunotherapeutic strategies for eradication of malignant stem cells in chronic myeloid leukaemia. Cancer Immunol Immunother 2005;54: 297-306.
71. Jamieson CH, Ailles LE, Dylla SJ, et al. Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. N Engl J Med 2004;351:657-67.
72. Gorre ME, Mohammed M, Ellwood K, et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 2001;293:876-80.
73. Modi H, McDonald T, Chu S, Yee JK, Forman SJ, Bhatia R. Role of BCR/ABL gene-expression levels in determining the phenotype and imatinib sensitivity of transformed human hematopoietic cells. Blood 2007;109:5411-21.
74. Hochhaus A, Kreil S, Corbin AS, et al. Molecular and chromosomal mechanisms of resistance to imatinib (STI571) therapy. Leukemia 2002;16: 2190-6.
75. Barnes DJ, Palaiologou D, Panousopoulou E, et al. Bcr-Abl expression levels determine the rate of development of resistance to imatinib mesylate in chronic myeloid leukemia. Cancer Res 2005;65: 8912-9.
76. Quintas-Cardama A, Kantarjian HM, Cortes JE. Mechanisms of primary and secondary resistance to imatinib in chronic myeloid leukemia. Cancer Control 2009;16:122-31.
77. Nicolini FE, Corm S, Le QH, et al. Mutation status and clinical outcome of 89 imatinib mesylateresistant chronic myelogenous leukemia patients: a retrospective analysis from the French intergroup of CML (Fi(phi)-LMC GROUP). Leukemia 2006;20:1061-6.
78. 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.
79. Nicolini FE, Hayette S, Corm S, et al. Clinical outcome of 27 imatinib mesylate-resistant chronic myelogenous leukemia patients harboring a T315I BCR-ABL mutation. Haematologica 2007;92:1238-41.
80. Soverini S, Colarossi S, Gnani A, et al. Contribution of ABL kinase domain mutations to imatinib resistance in different subsets of Philadelphiapositive patients: by the GIMEMA Working Party on Chronic Myeloid Leukemia. Clin Cancer Res 2006;12:7374-9.
81. Branford S, Rudzki Z, Walsh S, et al. Detection of BCR-ABL mutations in patients with CML treated with imatinib is virtually always accompanied by clinical resistance, and mutations in the ATP phosphate-binding loop (Ploop) are associated with a poor prognosis. Blood 2003;102:276-83.
82. Griswold IJ, MacPartlin M, Bumm T, et al. Kinase domain mutants of Bcr-Abl exhibit altered transformation potency, kinase activity, and substrate utilization, irrespective of sensitivity to imatinib. Mol Cell Biol 2006;26:6082-93.
83. Soverini S, Martinelli G, Rosti G, et al. ABL mutations in late chronic phase chronic myeloid leukemia patients with up-front cytogenetic resistance to imatinib are associated with a greater likelihood of progression to blast crisis and shorter survival: a study by the GIMEMA Working Party on Chronic Myeloid Leukemia. J Clin Oncol 2005;23:4100-9.
84. 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.
85. Roche-Lestienne C, Soenen-Cornu V, Grardel-Duflos N, et al. Several types of mutations of the Abl gene can be found in chronic myeloid leukemia patients resistant to STI571, and they can pre-exist to the onset of treatment. Blood 2002; 100:1014-8.
86. Khorashad JS, Anand M, Marin D, et al. The presence of a BCR-ABL mutant allele in CML does not always explain clinical resistance to imatinib. Leukemia 2006;20:658-63.
87. Willis SG, Lange T, Demehri S, et al. Highsensitivity 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.
88. Skaggs BJ, Gorre ME, Ryvkin A, et al. Phosphorylation of the ATP-binding loop directs oncogenicity of drug-resistant BCR-ABL mutants. Proc Natl Acad Sci U S A 2006;103:19466-71.
89. O'Hare T, Eide CA, Deininger MW. Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for chronic myeloid leukemia. Blood 2007;110:2242-9.
90. Shah NP, Skaggs BJ, Branford S, et al. Sequential ABL kinase inhibitor therapy selects for compound drug-resistant BCR-ABL mutations with altered oncogenic potency. J Clin Invest 2007;117:2562-9.
91. 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.
92. Khorashad JS, Milojkovic D, Mehta P, et al. In vivo kinetics of kinase domain mutations in CML patients treated with dasatinib after failing imatinib. Blood 2008;111:2378-81.
93. Stagno F, Stella S, Berretta S, et al. Sequential mutations causing resistance to both Imatinib Mesylate and Dasatinib in a chronic myeloid leukaemia patient progressing to lymphoid blast crisis. Leuk Res 2008;32:673-4.
94. 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.
95. Soverini S, Gnani A, Colarossi S, et al. Philadelphia-positive patients who already harbor imatinib-resistant Bcr-Abl kinase domain mutations have a higher likelihood of developing additional mutations associated with resistance to second- or third-line tyrosine kinase inhibitors. Blood 2009;114:2168-71.
96. Garg RJ, Kantarjian H, O'Brien S, Quintas-Cardama A, Faderl S, Estrov Z, et al. The use of nilotinib or dasatinib after failure to two prior tyrosine kinase inhibitors (TKI): long-term follow-up. Blood 2009, Epub 2009 Sep 3.
97. 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.
98. 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.
99. de Lavallade H, Khorashad JS, Davis HP, et al. Interferon-alpha or homoharringtonine as salvage treatment for chronic myeloid leukemia patients who acquire the T315I BCR-ABL mutation. Blood 2007;110:2779-80.
100. Apperley JF. Part I: mechanisms of resistance to imatinib in chronic myeloid leukaemia. Lancet Oncol 2007;8:1018-29.