• 1
    Faderl S, Talpaz M, Estrov Z, O'Brien S, Kurzrock R, Kantarjian HM. The biology of chronic myeloid leukemia. N Engl Med. 1999; 341: 164172.
  • 2
    Goldman JM, Melo JV. Chronic myeloid leukemia-advances in biology and new approaches to treatment. N Engl J Med. 2003; 349: 14511464.
  • 3
    Kantarjian HM, Cortes JE, O'Brien S, et al. Long-term survival benefit and improved complete cytogenetic and molecular response rates with imatinib mesylate in Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia after failure of interferon-alpha. Blood. 2004; 104: 19791988.
  • 4
    Kantarjian H, Sawyers C, Hochhaus A, et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl Med. 2002; 346: 645652.
  • 5
    Kantarjian H, Talpaz M, O'Brien S, et al. High-dose imatinib mesylate therapy in newly diagnosed Philadelphia chromosome-positive chronic phase chronic myeloid leukemia. Blood. 2004; 103: 28732878.
  • 6
    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: 9941004.
  • 7
    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: 14231432.
  • 8
    Cortes J, Talpaz M, O'Brien S, et al. Molecular responses in patients with chronic myelogenous leukemia in chronic phase treated with imatinib mesylate. Clin Cancer Res. 2005; 11: 34253432.
  • 9
    Gambacorti-Passerini CB, Gunby RH, Piazza R, Galietta A, Rostagno R, Scapozza L. Molecular mechanisms of resistance to imatinib in Philadelphia-hromosome-positive leukaemias. Lancet Oncol. 2003; 4: 7585.
  • 10
    Hochhaus A, Kreil S, Corbin AS, et al. Molecular and chromosomal mechanisms of resistance to imatinib (STI571) therapy. Leukemia. 2002; 16: 21902196.
  • 11
    Mandanas RA, Leibowitz DS, Gharehbaghi K, et al. Role of p21 RAS in p210 bcr-abl transformation of murine myeloid cells. Blood. 1993; 82: 18381847.
  • 12
    Puil L, Liu J, Gish G, et al. Bcr-Abl oncoproteins bind directly to activators of the Ras signalling pathway. EMBO J. 1994; 13: 764773.
  • 13
    Sawyers CL, McLaughlin J, Witte ON. Genetic requirement for Ras in the transformation of fibroblasts and hematopoietic cells by the Bcr-Abl oncogene. J Exp Med. 1995; 181: 307313.
  • 14
    Gelb MH. Protein prenylation, et cetera: signal transduction in two dimensions. Science. 1997; 275: 17501751.
  • 15
    Khosravi-Far R, Cox AD, Kato K, Der CJ. Protein prenylation: key to ras function and cancer intervention? Cell Growth Differ. 1992; 3: 461469.
  • 16
    Ashar HR, James L, Gray K, et al. Farnesyl transferase inhibitors block the farnesylation of CENP-E and CENP-F and alter the association of CENP-E with the microtubules. J Biol Chem. 2000; 275: 3045130457.
  • 17
    Beaupre DM, Kurzrock R. RAS and leukemia: from basic mechanisms to gene-directed therapy. J Clin Oncol. 1999; 17: 10711079.
  • 18
    Rowinsky EK, Windle JJ, Von Hoff DD. Ras protein farnesyltransferase: a strategic target for anticancer therapeutic development. J Clin Oncol. 1999; 17: 36313652.
  • 19
    Lackner MR, Kindt RM, Carroll PM, et al. Chemical genetics identifies Rab geranylgeranyl transferase as an apoptotic target of farnesyl transferase inhibitors. Cancer Cell. 2005; 7: 325336.
  • 20
    Liu M, Bryant MS, Chen J, et al. Antitumor activity of SCH 66336, an orally bioavailable tricyclic inhibitor of farnesyl protein transferase, in human tumor xenograft models and wap-ras transgenic mice. Cancer Res. 1998; 58: 49474956.
  • 21
    Peters DG, Hoover RR, Gerlach MJ, et al. Activity of the farnesyl protein transferase inhibitor SCH66336 against BCR/ABL-induced murine leukemia and primary cells from patients with chronic myeloid leukemia. Blood. 2001; 97: 14041412.
  • 22
    Reichert A, Heisterkamp N, Daley GQ, Groffen J. Treatment of Bcr/Abl-positive acute lymphoblastic leukemia in P190 transgenic mice with the farnesyl transferase inhibitor SCH66336. Blood. 2001; 97: 13991403.
  • 23
    Hoover RR, Mahon F-X, Melo JV, Daley GQ. Overcoming STI571 resistance with the farnesyl transferase inhibitor SCH66336. Blood. 2002; 100: 10681071.
  • 24
    Jorgensen HG, Allan EK, Graham SM, et al. Lonafarnib reduces the resistance of primitive quiescent CML cells to imatinib mesylate in vitro. Leukemia. 2005; 19: 11841191.
  • 25
    Borthakur G, Kantarjian H, Daley G, et al. Pilot study of lonafarnib, a farnesyl transferase inhibitor, in patients with chronic myeloid leukemia in the chronic or accelerated phase that is resistant or refractory to imatinib therapy. Cancer. 2006; 106: 346352.
  • 26
    Kantarjian HM, Keating MJ, Smith TL, Talpaz M, McCredie KB. Proposal for a simple synthesis prognostic staging system in chronic myelogenous leukemia. Am J Med. 1990; 88: 18.
  • 27
    Kantarjian HM, Smith T, O'Brien S, et al. Prolonged survival in chronic myelogenous leukemia after cytogenetic response to interferon- therapy. Ann Intern Med.. 1995; 122: 254261.
  • 28
    Gibaldi M, Perrier D. Pharmacokinetics. 2nd ed. New York: Dekker; 1982.
  • 29
    Peng B, Hayes M, Resta D, et al. Pharmacokinetics and pharmacodynamics of imatinib in a phase I trial with chronic myeloid leukemia patients. J Clin Oncol. 2004; 22: 935942.
  • 30
    Jabbour E, Kantarjian H, Cortes J. Clinical activity of farnesyl transferase inhibitors in hematologic malignancies: possible mechanisms of action. Leuk Lymphoma. 2004; 45: 21872195.
  • 31
    Cortes J, Garcia-Manero G, O'Brien S, et al. Phase I study of Imatinib and Tipifarnib (Zarnestra, R115777) in patients with chronic myeloid leukemia in chronic phase refractory to imatinib. Blood. 2003; 102: 909a. Abstract 3383.
  • 32
    Graham SM, Jorgensen HG, Allan E, et al. Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to STI571 in vitro. Blood. 2002; 99: 319325.
  • 33
    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: 45324539.
  • 34
    Copland M, Hamilton A, Allan EK, Brunton V, Holyoake TL. BMS-214662 targets quiescent chronic myeloid leukaemia stem cells and enhances the activity of both imatinib and dasatinib (BMS-354825). Blood. 2005; 106: 204a. Abstract 693.
  • 35
    Adjei AA, Erlichman C, Davis JN, et al. A Phase I trial of the farnesyl transferase inhibitor SCH66336: evidence for biological and clinical activity. Cancer Res. 2000; 60: 18711877.
  • 36
    Khuri FR, Glisson BS, Kim ES, et al. Phase I study of the farnesyltransferase inhibitor lonafarnib with paclitaxel in solid tumors. Clin Cancer Res. 2004; 10: 29682976.
  • 37
    Feldman EJ, Cortes J, Holyoake TL, et al. Continuous oral Lonafarnib (Sarasar™) for the treatment of patients with myelodysplastic syndrome. Blood. 2003; 102: 421a. Abstract 1531.
  • 38
    Kantarjian H, Giles F, Wunderle L, et al. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med. 2006; 354: 25422551.
  • 39
    Talpaz M, Shah NP, Kantarjian H, et al. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med. 2006; 354: 25312541.
  • 40
    Jabbour E, Cortes J, Kantarjian H, et al. Allogeneic stem cell transplantation for patients with chronic myeloid leukemia and acute lymphocytic leukemia after Bcr-Abl kinase mutation-related imatinib failure. Blood. 2006; 108: 14211423.
  • 41
    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: 45004505.
  • 42
    Shah NP, Tran C, Lee FY, Chen P, Norris D, Sawyers CL. Overriding imatinib resistance with a novel ABL kinase inhibitor. Science. 2004; 305: 399401.
  • 43
    Wong S, McLaughlin J, Cheng D, Zhang C, Shokat KM, Witte ON. Sole BCR-ABL inhibition is insufficient to eliminate all myeloproliferative disorder cell populations. Proc Natl Acad Sci U S A. 2004; 101: 1745617461.
  • 44
    Burgess MR, Skaggs BJ, Shah NP, Lee FY, Sawyers CL. Comparative analysis of two clinically active BCR-ABL kinase inhibitors reveals the role of conformation-specific binding in resistance. Proc Natl Acad Sci U S A. 2005; 102: 33953400.
  • 45
    Bradeen HA, Eide CA, O'Hare T, et al. Comparison of imatinib, dasatinib (BMS-354825), and nilotinib (AMN107) in an n-ethyl-n-nitrosourea (ENU) -based mutagenesis screen: high efficacy of drug combinations. Blood. 2006; 108: 23322338.
  • 46
    Shah NP, Nicoll JM, Branford S, et al. Molecular analysis of dasatinib resistance mechanisms in CML patients identifies novel BCR-ABL mutations predicted to retain sensitivity to imatinib: rationale for combination tyrosine kinase inhibitor therapy. Blood. 2005; 106: 318a. Abstract 1093.