252
Views
27
CrossRef citations to date
0
Altmetric
Review

Strategies for overcoming imatinib resistance in chronic myeloid leukemia

&
Pages 2310-2322 | Received 21 Aug 2007, Accepted 04 Sep 2007, Published online: 01 Jul 2009

References

  • Sawyers C L. Chronic myeloid leukemia. N Engl J Med 1999; 340: 1330–1340
  • Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, et al. Cancer statistics, 2006. CA Cancer J Clin 2006; 56: 106–130
  • Faderl S, Talpaz M, Estrov Z, O'Brien S, Kurzrock R, Kantarjian H M. The biology of chronic myeloid leukemia. N Engl J Med 1999; 341: 164–172
  • Druker B J, Tamura S, Buchdunger E, Ohno S, Segal G M, Fanning S, et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med 1996; 2: 561–566
  • O'Brien S G, Guilhot F, Larson R A, Gathmann I, Baccarani M, Cervantes F, 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
  • Druker B J, Guilhot F, O'Brien S G, Gathmann I, Kantarjian H, Gattermann N, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 2006; 355: 2408–2417
  • Sawyers C L, Hochhaus A, Feldman E, Goldman J M, Miller C B, Ottmann O G, 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: 3530–3539
  • Talpaz M, Silver R T, Druker B J, Goldman J M, Gambacorti-Passerini C, Guilhot F, et al. Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study. Blood 2002; 99: 1928–1937
  • Simonsson B. Beneficial effects of cytogenetic and molecular response on long-term outcome in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatinib (IM): update from the IRIS study. Blood (Suppl.) 2005; 106: 166
  • Hughes T P, Kaeda J, Branford S, Rudzki Z, Hochhaus A, Hensley M L, 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: 1423–1432
  • Muller M C, Gattermann N, Lahaye T, Deininger M W, Berndt A, Fruehauf S, et al. Dynamics of BCR-ABL mRNA expression in first-line therapy of chronic myelogenous leukemia patients with imatinib or interferon alpha/ara-C. Leukemia 2003; 17: 2392–2400
  • Druker B J, Guilhot F, O'Brien S, Larson N, on behalf of the IRIS. Long-term benefits of imatinib (IM) for patients newly diagnosed with chronic myelogenous leukemia in chronic phase (CML-CP): the 5-year update from the IRIS study. J Clin Oncol 2006; 24(18S)6506
  • Bocchia M, Forconi F, Lauria F. Emerging drugs in chronic myelogenous leukaemia. Expert Opin Emerg Drugs 2006; 11: 651–664
  • National Comprehensive Cancer Network (NCCN) [pdf on the Internet]. NCCN Clinical Practice Guidelines in Oncology: Chronic Myelogenous Leukemia. V.2.2007. NCCN, Jenkintown, PA, [updated 2006 cited; July 2007]. Available from: http://www.nccn.org/professionals/physician_gls/PDF/cml.pdf. Accessed March 2007
  • Baccarani M, Saglio G, Goldman J, Hochhaus A, Simonsson B, Appelbaum F, 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: 1809–1820
  • Mauro M J. Defining and managing imatinib resistance. Hematol Am Soc Hematol Educ Program 2006; 219–225
  • Litzow M R. Imatinib resistance: obstacles and opportunities. Arch Pathol Lab Med 2006; 130: 669–679
  • Mauro M J, Deininger M W. Chronic myeloid leukemia in 2006: a perspective. Haematologica 2006; 91: 152
  • Hochhaus A, Erben P, Ernst T, Mueller M C. Resistance to targeted therapy in chronic myelogenous leukemia. Semin Hematol 2007; 44: 15–24
  • Hochhaus A, La R P. Imatinib therapy in chronic myelogenous leukemia: strategies to avoid and overcome resistance. Leukemia 2004; 18: 1321–1331
  • Shah N P, Nicoll J M, Nagar B, Gorre M E, Paquette R L, Kuriyan J, et al. 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 2002; 2: 117–125
  • Hughes T, Deininger M, Hochhaus A, Branford S, Radich J, Kaeda J, 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
  • Deininger M, Buchdunger E, Druker B J. The development of imatinib as a therapeutic agent for chronic myeloid leukemia. Blood 2005; 105: 2640–2653
  • Branford S, Rudzki Z, Walsh S, Parkinson I, Grigg A, Szer J, 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 (P-loop) are associated with a poor prognosis. Blood 2003; 102: 276–283
  • La Rosee P, Corbin A S, Stoffregen E P, Deininger M W, Druker B J. Activity of the Bcr-Abl kinase inhibitor PD180970 against clinically relevant Bcr-Abl isoforms that cause resistance to imatinib mesylate (Gleevec, STI571). Cancer Res 2002; 62: 7149–7153
  • Weisberg E, Manley P W, Cowan-Jacob S W, Hochhaus A, Griffin J D. Second generation inhibitors of BCR-ABL for the treatment of imatinib-resistant chronic myeloid leukaemia. Nat Rev Cancer 2007; 7: 345–356
  • Soverini S, Martinelli G, Rosti G, Bassi S, Amabile M, Poerio A, 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: 4100–4109
  • Hochhaus A, Ernst T, Erben P, Mueller M C, Emig M, Kreil S, et al. Long term observation of CML patients after imatinib resistance associated with BCR-ABL mutations. Blood (Suppl.) 2005; 106, 1086
  • Jabbour E, Kantarjian H, Jones D, Talpaz M, Bekele N, O'Brien S, et al. Frequency and clinical significance of BCR-ABL mutations in patients with chronic myeloid leukemia treated with imatinib mesylate. Leukemia 2006; 20: 1767–1773
  • Shah N, Skaggs B, Branford S, Hughes T P, Nicoll J M, Paquette R L, et al. Sequential kinase inhibitor therapy in CML patients can select for cells harboring compound BCR-ABL kinase domain mutations with increased oncogenic potency: rationale for early combination therapy of ABL kinase inhibitors. Blood (Suppl.) 2006; 108: 751
  • Hochhaus A, Kreil S, Corbin A S, La R P, Muller M C, Lahaye T, et al. Molecular and chromosomal mechanisms of resistance to imatinib (STI571) therapy. Leukemia 2002; 16: 2190–2196
  • Roumiantsev S, Shah N P, Gorre M E, Nicoll J, Brasher B B, Sawyers C L, et al. Clinical resistance to the kinase inhibitor STI-571 in chronic myeloid leukemia by mutation of Tyr-253 in the Abl kinase domain P-loop. Proc Natl Acad Sci USA 2002; 99: 10700–10705
  • Azam M, Latek R R, Daley G Q. Mechanisms of autoinhibition and STI-571/imatinib resistance revealed by mutagenesis of BCR-ABL. Cell 2003; 112: 831–843
  • Gorre M E, Mohammed M, Ellwood K, Hsu N, Paquette R, Rao P N, et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 2001; 293: 876–880
  • Danhauser-Riedl S, Warmuth M, Druker B J, Emmerich B, Hallek M. Activation of Src kinases p53/56lyn and p59hck by p210bcr/abl in myeloid cells. Cancer Res 1996; 56: 3589–3596
  • Warmuth M, Bergmann M, Priess A, Hauslmann K, Emmerich B, Hallek M. 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 1997; 272: 33260–33270
  • Roginskaya V, Zuo S, Caudell E, Nambudiri G, Kraker A J, Corey S J. Therapeutic targeting of Src-kinase Lyn in myeloid leukemic cell growth. Leukemia 1999; 13: 855–861
  • Lionberger J M, Wilson M B, Smithgall T E. Transformation of myeloid leukemia cells to cytokine independence by Bcr-Abl is suppressed by kinase-defective Hck. J Biol Chem 2000; 275: 18581–18585
  • Donato N J, Wu J Y, Stapley J, Gallick G, Lin H, Arlinghaus R, et al. BCR-ABL independence and LYN kinase overexpression in chronic myelogenous leukemia cells selected for resistance to STI571. Blood 2003; 101: 690–698
  • Dai Y, Rahmani M, Corey S J, Dent P, Grant S. A 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: 34227–34239
  • Hu Y, Swerdlow S, Duffy T M, Weinmann R, Lee F Y, 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 USA 2006; 103: 16870–16875
  • Meyn M A, III, Wilson M B, Abdi F A, Fahey N, Schiavone A P, Wu J, et al. Src family kinases phosphorylate the Bcr-Abl SH3-SH2 region and modulate Bcr-Abl transforming activity. J Biol Chem 2006; 281: 30907–30916
  • Donato N J, Wu J Y, Stapley J, Lin H, Arlinghaus R, Aggarwal B B, et al. Imatinib mesylate resistance through BCR-ABL independence in chronic myelogenous leukemia. Cancer Res 2004; 64: 672–677
  • Donato N J, Wu J, Kong L Y, Meng F, Lee F Y, Talpaz M. Constitutive activation of SRC-family kinases in chronic myelogenous leukemia patients resistant to imatinib mesylate in the absence of BCR-ABL mutations: a rationale for use of SRC/ABL dual kinase inhibitor-based therapy. Blood (Suppl.) 2005; 106: 1087
  • Gambacorti-Passerini C, Barni R, le C P, Zucchetti M, Cabrita G, Cleris L, et al. Role of α-1 acid glycoprotein in the in vivo resistance of human BCR-ABL(+) leukemic cells to the abl inhibitor STI571. J Natl Cancer Inst 2000; 92: 1641–1650
  • Larghero J, Leguay T, Mourah S, Madelaine-Chambrin I, Taksin A L, Raffoux E, et al. Relationship between elevated levels of the α-1 acid glycoprotein in chronic myelogenous leukemia in blast crisis and pharmacological resistance to imatinib (Gleevec) in vitro and in vivo. Biochem Pharmacol 2003; 66: 1907–1913
  • le Coutre P, Kreuzer K A, Na I K, Lupberger J, Holdhoff M, Appelt C, et al. Determination of α-1 acid glycoprotein in patients with Ph+ chronic myeloid leukemia during the first 13 weeks of therapy with STI571. Blood Cells Mol Dis 2002; 28: 75–85
  • Mahon F X, Deininger M W, Schultheis B, Chabrol J, Reiffers J, Goldman J M, 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: 1070–1079
  • Thomas J, Wang L, Clark R E, Pirmohamed M. Active transport of imatinib into and out of cells: implications for drug resistance. Blood 2004; 104: 3739–3745
  • Illmer T, Schaich M, Platzbecker U, Freiberg-Richter J, Oelschlagel U, von B M, et al. P-glycoprotein-mediated drug efflux is a resistance mechanism of chronic myelogenous leukemia cells to treatment with imatinib mesylate. Leukemia 2004; 18: 401–408
  • Ling V. Multidrug resistance: molecular mechanisms and clinical relevance. Cancer Chemother Pharmacol 1997; 40: S3–S8
  • White D L, Saunders V A, Dang P, Engler J, Zannettino A C, Cambareri A C, 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
  • Kantarjian H M, Talpaz M, Giles F, O'Brien S, Cortes J. New insights into the pathophysiology of chronic myeloid leukemia and imatinib resistance. Ann Intern Med 2006; 145: 913–923
  • Kantarjian H M, Talpaz M, O'Brien S, Giles F, Garcia-Manero G, Faderl S, et al. Dose escalation of imatinib mesylate can overcome resistance to standard-dose therapy in patients with chronic myelogenous leukemia. Blood 2003; 101: 473–475
  • Zonder J A, Pemberton P, Brandt H, Mohamed A N, Schiffer C A. The effect of dose increase of imatinib mesylate in patients with chronic or accelerated phase chronic myelogenous leukemia with inadequate hematologic or cytogenetic response to initial treatment. Clin Cancer Res 2003; 9: 2092–2097
  • O'hare T, Walters D K, Stoffregen E P, Jia T, Manley P W, Mestan J, 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: 4500–4505
  • Shah N P, Tran C, Lee F Y, Chen P, Norris D, Sawyers C L. Overriding imatinib resistance with a novel ABL kinase inhibitor. Science 2004; 305: 399–401
  • Tokarski J S, Newitt J A, Chang C Y, Cheng J D, Wittekind M, Kiefer S E, et al. The structure of dasatinib (BMS-354825) bound to activated ABL kinase domain elucidates its inhibitory activity against imatinib-resistant ABL mutants. Cancer Res 2006; 66: 5790–5797
  • Jabbour E, Cortes J, Giles F, O'Brien S, Kantarjian H. The clinical challenge of imatinib resistance in chronic myeloid leukemia: emerging strategies with new targeted agents. Targ Oncol 2006; 1: 186–196
  • Jabbour E, Jones D, Kantarjian H, O'Brien S, Garcia-Manero G, Giles F, et al. Dynamics of BCR-ABL kinase domain mutations in patients with chronic myeloid leukemia (CML) after treatment with one, two or three tyrosine kinase inhibitors (TKI). Blood (Suppl.) 2006; 108: 750
  • Soverini S, Martinelli G, Colarossi S, Gnani A, Castagnetti F, Rosti G, et al. Mutations at residues 315 and 317 in the ABL kinase domain are the main cause of resistance to dasatinib in philadelphia-positive (Ph+) leukemia patients (pts). Blood (Suppl.) 2006; 108: 836
  • Lee F Y, Lombardo L, Camuso A, Castaneda S, Fager K, Flefleh C, et al. BMS-354825 potently inhibits multiple selected oncogenic tyrosine kinases and possesses broad-spectrum antitumor activities in vitro and in vivo. Proceedings of the 2005 American Association for Cancer Research Annual Meeting, Anaheim, CA, April, 16 – 202005, Abstract 675
  • Lombardo L J, Lee F Y, Chen P, Norris D, Barrish J C, Behnia K, et al. Discovery of N-(2-chloro-6-methyl-phenyl)-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: 6658–6661
  • Nam S, Kim D, Cheng J Q, Zhang S, Lee J H, Buettner R, et al. Action of the Src family kinase inhibitor, dasatinib (BMS-354825), on human prostate cancer cells. Cancer Res 2005; 65: 9185–9189
  • Schittenhelm M M, Shiraga S, Schroeder A, Corbin A S, Griffith D, Lee F Y, et al. Dasatinib (BMS-354825), a dual SRC/ABL kinase inhibitor, inhibits the kinase activity of wild-type, juxtamembrane, and activation loop mutant KIT isoforms associated with human malignancies. Cancer Res 2006; 66: 473–481
  • Talpaz M, Shah N P, Kantarjian H, Donato N, Nicoll J, Paquette R, et al. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med 2006; 354: 2531–2541
  • Guilhot F, Apperley J, Facon T, Niederwieser D, Gambacorti C, Fischer T, et al. Dasatinib induces durable cytogenetic responses in patients with chronic-phase CML with resistance or intolerance to imatinib: updated results of the CA180013 (START-C) trial. Haematologica 2007; 92(Suppl 1)128, (Abstract 0358)
  • Cortes J, Kim D W, Guilhot F, Rosti G, Silver R T, Gollerkeri A, et al. Dasatinib (SPRYCEL) in patients (pts) with chronic myelogenous leukemia in accelerated phase (AP-CML) that is imatinib-resistant (im-r) or -intolerant (im-i): updated results of the CA180-005 START-A phase II study. Blood (Suppl.) 2006; 108: 2160
  • Martinelli G, Hochhaus A, Coutre S, Apperley J F, Shah N, Gollerkeri A, et al. Dasatinib (SPRYCEL) efficacy and safety in patients (pts) with chronic myelogenous leukemia in lymphoid (CML-LB) or myeloid blast (CML-MB) phase who are imatinib-resistant (im-r) or -intolerant (im-i). Blood (Suppl.) 2006; 108: 745
  • Ottmann O, Hochhaus A, Saglio G, Paquette R, Simonsson B, Porkka K, et al. Dasatinib induces rapid and durable responses in patients with Ph+ ALL resistant or intolerant to imatinib: updated results from CA180015 (START-L) trial. Haematologica 2007; 92(Suppl 1)9–10, Abstract 0026
  • Shah N P, Kim D W, Kantarjian H, Rousselot P, Dorlhiac-Llacer P E, Milone J, et al. Dasatinib 50 mg or 70 mg BID compared to 100 mg or 140 mg QD in patients with CML in chronic phase (CP) who are resistant or intolerant to imatinib: one-year results of CA180034. J Clin Oncol (ASCO Ann Meeting Proc) Part I 2007, Suppl, Abstract 7004
  • Baccarani M, Kantarjian H M, Apperley J F, Lipton J H, Druker B, Countouriotis A, et al. Efficacy of dasatinib (SPRYCEL) in patients (pts) with chronic phase chronic myelogenous leukemia (CP-CML) resistant to or intolerant of imatinib: updated results of the CA180013 START-C phase II study. Blood (Suppl.) 2006; 108: 164
  • Hochhaus A, Kantarjian H M, Baccarani M, Lipton J H, Apperley J F, Druker B J, et al. Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy. Blood 2007; 109: 2303–2309
  • Kantarjian H, Pasquini R, Hamerschlak N, Rousselot P, Holowiecki J, Jootar S, et al. Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia after failure of first-line imatinib: a randomized phase 2 trial. Blood 2007; 109: 5143–5150
  • Hochhaus A, Kim D W, Rousselot P, Kantarjian H M, Charbonnier A, Heim D, et al. Dasatinib dose and schedule optimization in chronic-phase CML resistant or intolerant to imatinib: results from a randomized phase-III trial (CA180034). Haematologica 2007; 92(Suppl 1)128–129, Abstract 0359
  • Anstrom K J, Reed S D, Allen A S, Glendenning G A, Schulman K A. Long-term survival estimates for imatinib versus interferon-alpha plus low-dose cytarabine for patients with newly diagnosed chronic-phase chronic myeloid leukemia. Cancer 2004; 101: 2584–2592
  • Kantarjian H M, O'Brien S, Cortes J E, Shan J, Giles F J, Rios M B, et al. Complete cytogenetic and molecular responses to interferon-α-based therapy for chronic myelogenous leukemia are associated with excellent long-term prognosis. Cancer 2003; 97: 1033–1041
  • Roy L, Guilhot J, Krahnke T, Guerci-Bresler A, Druker B J, Larson R A, 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 3 trials. Blood 2006; 108: 1478–1484
  • Kantarjian H M, Talpaz M, O'Brien S, Smith T L, Giles F J, Faderl S, et al. Imatinib Mesylate for Philadelphia chromosome-positive, chronic-phase myeloid leukemia after failure of interferon-α: follow-up results. Clin Cancer Res 2002; 8: 2177–2187
  • Kantarjian H, Schiffer C, Sawyers C L, Hochhaus A, Guilhot F, Niederwieser D W, et al. Imatinib (Gleevec) maintains favorable long-term outcomes in chronic-phase chronic myeloid leukemia (CML) for patients failing interferon-α (IFN) follow-up of a phase II study. Blood (Suppl.) 2003; 102: 3368
  • Talpaz M, Goldman J, Sawyers C, Hochhaus A, Silver R T, et al. High dose imatinib (STI571, Gleevec) provides durable long-term outcomes for patients (Pts) with chronic myeloid leukemia (CML) in accelerated phase (AP) or myeloid blast crisis (BC): follow-up of the phase II studies. Blood (Suppl.) 2003; 102: 3369
  • Marin D, Marktel S, Bua M, Szydlo R M, Franceschino A, Nathan I, et al. Prognostic factors for patients with chronic myeloid leukaemia in chronic phase treated with imatinib mesylate after failure of interferon alfa. Leukemia 2003; 17: 1448–1453
  • Cowan-Jacob S W, Fendrich G, Floersheimer A, Furet P, Liebetanz J, Rummel G, et al. Structural biology contributions to the discovery of drugs to treat chronic myelogenous leukaemia. Acta Crystallogr D Biol Crystallogr 2007; 63: 80–93
  • Manley P W, Bruggen J, Fabbro D, Martiny-Baron G, Meyer T. Extended kinase profiling of the Bcr-Abl inhibitor nilotinib. Proceedings of the 2007 American Association for Cancer Research Annual Meeting, Los Angeles, CA, April, 14 – 182007, Abstract 3249
  • Weisberg E, Manley P W, Breitenstein W, Bruggen J, Cowan-Jacob S W, Ray A, et al. Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl. Cancer Cell 2005; 7: 129–141
  • Jensen M R, Bruggen J, Dilea C, Mestan J, Manley P W. AMN107: efficacy of the selective Bcr-Abl tyrosine kinase inhibitor in a murine model of chronic myelogenous leukemia. Proceedings of the 2006 American Association for Cancer Research Annual Meeting, Washington, DC, April, 1 – 52006, Abstract 261
  • Kantarjian H, Giles F, Wunderle L, Bhalla K, O'Brien S, Wassmann B, et al. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med 2006; 354: 2542–2451
  • Rosti G, le Coutre P, Bhalla K, Giles F, Ossenkoppele G, Hochhaus A, et al. A phase II study of nilotinib administered to imatinib resistant and intolerant patients with chronic myelogenous leukemia (CML) in chronic phase (CP). J Clin Oncol (ASCO Ann Meeting Proc Part I) 2007; 25(18 Suppl), Abstract
  • le Coutre P, Gattermann N, Hochhaus A, Larson R, Weitzman A, Haque A, et al. A phase II study of nilotinib administered to imatinib resistant or intolerant patients with chronic myelogenous leukemia (CML) in accelerated phase (AP). J Clin Oncol (ASCO Ann Meeting Proc Part I) 2007; 25(18 Suppl), Abstract 7026
  • Larson R, Ottmann O, Kantarjian H, le Coutre P, Baccarani M, Weitzman A, et al. A phase II study of nilotinib administered to imatinib resistant or intolerant patients with chronic myelogenous leukemia (CML) in blast crisis (BC) or relapsed/refractory Ph+ acute lymphoblastic leukemia (ALL). J Clin Oncol (ASCO Ann Meeting Proc Part I) 2007; 25(18 Suppl), Abstract 7040
  • Mueller M C, Branford S, Radich J, Kim D W, Martinelli G, Saglio G, et al. Response dynamics to nilotinib depend on the type of BCR-ABL mutations in patients with chronic myelogenous leukemia (CML) after imatinib failure. J Clin Oncol (ASCO Ann Meeting Proc) 2007; 25(18 Suppl), Abstract 7024
  • Giles F J, le Coutre P, Bhalla K, Rosti G, Ossenkoppele G, Alimena G, et al. A phase II study of nilotinib administered to patients with imatinib resistant or intolerant chronic myelogenous leukemia (CML) in chronic phase (CP), accelerated phase (AP) or blast crisis (BC) who also failed dasatinib. J Clin Oncol (ASCO Ann Meeting Proc Part I) 2007; 25(18 Suppl), Abstract 7038
  • Golas J M, Arndt K, Etienne C, Lucas J, Nardin D, Gibbons J, et al. SKI-606, a 4-anilino-3-quinolinecarbonitrile dual inhibitor of Src and Abl kinases, is a potent antiproliferative agent against chronic myelogenous leukemia cells in culture and causes regression of K562 xenografts in nude mice. Cancer Res 2003; 63: 375–381
  • Cortes J, Kantarjian H M, Baccarani M, Brummendorf T, Liu D, Ossenkoppele G, et al. A phase 1/2 study of SKI-606, a dual Inhibitor of Src and Abl kinases, in adult patients with Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia (CML) or acute lymphocytic leukemia (ALL) relapsed, refractory or intolerant of imatinib. Blood (Suppl.) 2006; 108: 168
  • Kimura S, Naito H, Segawa H, Kuroda J, Yuasa T, Sato K, et al. NS-187, a potent and selective dual Bcr-Abl/Lyn tyrosine kinase inhibitor, is a novel agent for imatinib-resistant leukemia. Blood 2005; 106: 3948–3954
  • Naito H, Kimura S, Nakaya Y, Naruoka H, Kimura S, Ito S, et al. In vivo antiproliferative effect of NS-187, a dual Bcr-Abl/Lyn tyrosine kinase inhibitor, on leukemic cells harbouring Abl kinase domain mutations. Leuk Res 2006; 30: 1443–1446
  • Carter T A, Wodicka L M, Shah N P, Velasco A M, Fabian M A, Treiber D K, et al. Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases. Proc Natl Acad Sci USA 2005; 102: 11011–11016
  • Harrington E A, Bebbington D, Moore J, Rasmussen R K, Jose-Adeogun A O, Nakayama T, et al. VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. Nat Med 2004; 10: 262–267
  • Young M A, Shah N P, Chao L H, Seeliger M, Milanov Z V, Biggs W H, III, et al. Structure of the kinase domain of an imatinib-resistant Abl mutant in complex with the Aurora kinase inhibitor VX-680. Cancer Res 2006; 66: 1007–1014
  • Giles F J, Cortes J, Jones D, Bergstrom D, Kantarjian H, Freedman S J. MK-0457, a novel kinase inhibitor, is active in patients with chronic myeloid leukemia or acute lymphocytic leukemia with the T315I BCR-ABL mutation. Blood 2007; 109: 500–502
  • Shah N P, Skaggs B, Branford S, Hughes T P, Nicoll J M, Paquette R L, et al. The most common Dasatinib-resistant BCR-ABL Kinase domain mutations in patients with chronic myeloid leukemia are sensitive to VX-680: rationale for early combination kinase inhibitor therapy. Blood (Suppl.) 2006; 108: 2175
  • Zhang W. Inhibition of the drug-resistant T315I mutant of BCR-Abl. Eur J Cancer 2006, Suppl 4, Abstract 54
  • Shakespeare W C, Wang F, Xu Q, Zhu X, Narasimham N, Metcalf C A, et al. Orally active inhibitors of the imatinib resistant Bcr-Abl mutant T315I. Blood (Suppl.) 2006; 108: 2180
  • Weisberg E, Manley P, Mestan J, Cowan-Jacob S, Ray A, Griffin J D. AMN107 (nilotinib): a novel and selective inhibitor of BCR-ABL. Br J Cancer 2006; 94: 1765–1769

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.