Targeted CML therapy: Controlling drug resistance, seeking cure

Current Opinion in Genetics and Development

Volumn 16, Issue 1, 2006, Pages 92-99

  O'Hare, Thomas ^a   Corbin, Amie S ^a   Druker, Brian J ^a  

^a HOWARD HUGHES MEDICAL INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BCR ABL PROTEIN; DASATINIB; IMATINIB; NILOTINIB; PHOSPHOTRANSFERASE INHIBITOR;

CANCER CONTROL; CANCER STEM CELL; CANCER THERAPY; CHRONIC MYELOID LEUKEMIA; CLINICAL TRIAL; DRUG INHIBITION; DRUG POTENTIATION; DRUG RESISTANCE; HUMAN; PRIORITY JOURNAL; REVIEW;

ANTINEOPLASTIC AGENTS; DRUG RESISTANCE, NEOPLASM; HUMANS; LEUKEMIA, MYELOID, CHRONIC; MODELS, BIOLOGICAL; PIPERAZINES; POINT MUTATION; PROTEIN KINASE INHIBITORS; PROTEIN-TYROSINE KINASES; PYRIMIDINES; THIAZOLES; TUMOR STEM CELLS;

EID: 30644462841     PISSN: 0959437X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.gde.2005.11.002     Document Type: Review

References (58)

1. M.W. Deininger, J.M. Goldman, and J.V. Melo The molecular biology of chronic myeloid leukemia Blood 96 2000 3343 3356
2. S. Wong, and O.N. Witte The BCR-ABL story: bench to bedside and back Annu Rev Immunol 22 2004 247 306
3. B. Calabretta, and D. Perrotti The biology of CML blast crisis Blood 103 2004 4010 4022
4. M. Deininger, E. Buchdunger, and B.J. Druker The development of imatinib as a therapeutic agent for chronic myeloid leukemia Blood 105 2005 2640 2653
5. T.P. Hughes, J. Kaeda, S. Branford, Z. Rudzki, A. Hochhaus, M.L. Hensley, I. Gathmann, A.E. Bolton, I.C. van Hoomissen, and J.M. Goldman Frequency of major molecular responses to imatinib or interferon α plus cytarabine in newly diagnosed chronic myeloid leukemia N Engl J Med 349 2003 1423 1432
6. M. Copland, A.R. Fraser, S.J. Harrison, and T.L. Holyoake Targeting the silent minority: emerging immunotherapeutic strategies for eradication of malignant stem cells in chronic myeloid leukaemia Cancer Immunol Immunother 54 2005 297 306
7. B.J. Huntly, and D.G. Gilliland Leukaemia stem cells and the evolution of cancer-stem-cell research Nat Rev Cancer 5 2005 311 321 This review begins with an historical account of how we came to our current view of leukemic stem cells then covers differences among leukemic stem cells, normal hematopoietic stem cells and committed progenitors that have acquired self-renewal capabilities. Possible approaches for selective targeting of leukemic stem cells are addressed.
8. L.J. Elrick, H.G. Jorgensen, J.C. Mountford, and T.L. Holyoake Punish the parent not the progeny Blood 105 2005 1862 1866 Short, highly informative review covering key issues in CML disease persistence.
9. M. Dean, T. Fojo, and S. Bates Tumor stem cells and drug resistance Nat Rev Cancer 5 2005 275 284 This review includes an up-to-date discussion of drug transporters in stem cells.
10. M.E. O'Dwyer, M.J. Mauro, C. Blasdel, M. Farnsworth, G. Kurilik, Y.C. Hsieh, M. Mori, and B.J. Druker Clonal evolution and lack of cytogenetic response are adverse prognostic factors for hematologic relapse of chronic phase CML patients treated with imatinib mesylate Blood 103 2004 451 455
11. C. Yoshida, and J.V. Melo Biology of chronic myeloid leukemia and possible therapeutic approaches to imatinib-resistant disease Int J Hematol 79 2004 420 433
12. V. Nardi, M. Azam, and G.Q. Daley Mechanisms and implications of imatinib resistance mutations in BCR-ABL Curr Opin Hematol 11 2004 35 43
13. A. Hochhaus, and P. La Rosée Imatinib therapy in chronic myelogenous leukemia: strategies to avoid and overcome resistance Leukemia 18 2004 1321 1331
14. S.W. Cowan-Jacob, V. Guez, G. Fendrich, J.D. Griffin, D. Fabbro, P. Furet, J. Liebetanz, J. Mestan, and P.W. Manley Imatinib (STI571) resistance in chronic myelogenous leukemia: molecular basis of the underlying mechanisms and potential strategies for treatment Mini Rev Med Chem 4 2004 285 299
15. H. Daub, K. Specht, and A. Ullrich Strategies to overcome resistance to targeted protein kinase inhibitors Nat Rev Drug Discov 3 2004 1001 1010
16. E. Weisberg, P.W. Manley, W. Breitenstein, J. Brüggen, A. Ray, S.W. Cowan-Jacob, D. Fabbro, G. Fendrich, E. Hall-Meyers, and B.J. Huntly Characterization of AMN107, a selective inhibitor of wild-type and mutant Bcr-Abl Cancer Cell 7 2005 129 141 This first report describing the new imatinib family member AMN107 includes a crystallographic analysis of AMN107 in complex with the imatinib-resistant mutant ABL(M351T). Comparison of this structure with the imatinib-ABL complex provides a structural rationale for the improved ABL-binding affinity of AMN107.
17. T. O'Hare, D.K. Walters, E.P. Stoffregen, T. Jia, P.W. Manley, J. Mestan, S.W. Cowan-Jacob, F.Y. Lee, M.C. Heinrich, and M. Deininger In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants Cancer Res 65 2005 4500 4505 This study uses cellular and biochemical assays to directly compare the effectiveness of imatinib, AMN107 and dasatinib (BMS-354825) against a broad panel of imatinib-resistant BCR-ABL mutants.
18. J. Cools, E.H. Stover, I. Wlodarska, P. Marynen, and D.G. Gilliland The FIP1L1-PDGFRα kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia Curr Opin Hematol 11 2004 51 57
19. M. Debiec-Rychter, J. Cools, H. Dumez, R. Sciot, M. Stul, N. Mentens, H. Vranckx, B. Wasag, H. Prenen, and J. Roesel Mechanisms of resistance to imatinib mesylate in gastrointestinal stromal tumors and activity of the PKC412 inhibitor against imatinib-resistant mutants Gastroenterology 128 2005 270 279
20. N.P. Shah, C. Tran, F.Y. Lee, P. Chen, D. Norris, and C.L. Sawyers Overriding imatinib resistance with a novel ABL kinase inhibitor Science 305 2004 399 401 This study introduces the orally bio-available SRC/ABL kinase inhibitor dasatinib (BMS-354825) and demonstrates in vivo activity against BCR-ABL and the imatinib-resistant mutant BCR-ABL (M351T) in a mouse model of disease.
21. B. Nagar, W.G. Bornmann, P. Pellicena, T. Schindler, D.R. Veach, W.T. Miller, B. Clarkson, and J. Kuriyan Crystal structures of the kinase domain of c-Abl in complex with the small molecule inhibitors PD173955 and imatinib (STI-571) Cancer Res 62 2002 4236 4243
22. N. von Bubnoff, D.R. Veach, W.T. Miller, W. Li, J. Sanger, C. Peschel, W.G. Bornmann, B. Clarkson, and J. Duyster Inhibition of wild-type and mutant Bcr-Abl by pyrido-pyrimidine-type small molecule kinase inhibitors Cancer Res 63 2003 6395 6404
23. T. O'Hare, R. Pollock, E.P. Stoffregen, J.A. Keats, O.M. Abdullah, E.M. Moseson, V.M. Rivera, H. Tang, C.A. Metcalf III, and R.S. Bohacek Inhibition of wild-type and mutant Bcr-Abl by AP23464, a potent ATP-based oncogenic protein kinase inhibitor: implications for CML Blood 104 2004 2532 2539
24. S. Chu, H. Xu, N.P. Shah, D.S. Snyder, S.J. Forman, C.L. Sawyers, and R. Bhatia Detection of BCR-ABL kinase mutations in CD34+ cells from chronic myelogenous leukemia patients in complete cytogenetic remission on imatinib mesylate treatment Blood 105 2005 2093 2098
25. M. Azam, R.R. Latek, and G.Q. Daley Mechanisms of autoinhibition and STI-571/imatinib resistance revealed by mutagenesis of BCR-ABL Cell 112 2003 831 843
26. N. von Bubnoff, D.R. Veach, H. van der Kuip, W.E. Aulitzky, J. Sanger, P. Seipel, W.G. Bornmann, C. Peschel, B. Clarkson, and J. Duyster A cell-based screen for resistance of Bcr-Abl-positive leukemia identifies the mutation pattern for PD166326, an alternative Abl kinase inhibitor Blood 105 2005 1652 1659 This study introduces a cell-based method of identifying drug resistant BCR-ABL mutants. Ba-F3 cells transfected with wild type BCR-ABL were grown at high density in the presence of imatinib or the SRC/ABL inhibitor PD166326, and sub-lines were established from surviving colonies. In contrast to the method described by Azam et al. [25], mutations were confined to the BCR-ABL kinase domain.
27. M.R. Burgess, B.J. Skaggs, N.P. Shah, F.Y. Lee, and C.L. Sawyers Comparative analysis of two clinically active BCR-ABL kinase inhibitors reveals the role of conformation-specific binding in resistance Proc Natl Acad Sci USA 102 2005 3395 3400
28. T. O'Hare, D.K. Walters, E.P. Stoffregen, D.W. Sherbenou, M.C. Heinrich, M. Deininger, and B. Druker Combined Abl inhibitor therapy for minimizing drug resistance in CML: Src/Abl inhibitors are compatible with imatinib Clin Cancer Res 11 2005 6987 6993
29. N.L. Komarova, and D. Wodarz Drug resistance in cancer: principles of emergence and prevention Proc Natl Acad Sci USA 102 2005 9714 9719 A mathematical model that uses three measurable disease parameters to predict whether combination therapy is likely to reduce the incidence of drug resistance compared with the incidence after single-agent therapy. Cancers with low rates of tumor cell turnover and/or low tumor mutation rates fare better in this analysis than cancers with high turnover rates and/or high tumor mutation rates. For example, the model predicts that resistance in CML may be controllable with three drugs, whereas other cancers require ten or more non-cross-resistant drugs.
30. T.A. Carter, L.M. Wodicka, N.P. Shah, A.M. Velasco, M.A. Fabian, D.K. Treiber, Z.V. Milanov, C.E. Atteridge, W.H. Biggs III, and P.T. Edeen Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases Proc Natl Acad Sci USA 102 2005 11011 11016
31. T. O'Hare, and B. Druker BIRB-796 is not an effective ABL(T315I) inhibitor Nat Biotechnol 23 2005 1209 1210
32. K. Gumireddy, S.J. Baker, S.C. Cosenza, P. John, A.D. Kang, K.A. Robell, M.V. Reddy, and E.P. Reddy A non-ATP-competitive inhibitor of BCR-ABL overrides imatinib resistance Proc Natl Acad Sci USA 102 2005 1992 1997
33. B. Nagar, O. Hantschel, M.A. Young, K. Scheffzek, D. Veach, W. Bornmann, B. Clarkson, G. Superti-Furga, and J. Kuriyan Structural basis for the autoinhibition of c-Abl tyrosine kinase Cell 112 2003 859 871
34. O. Hantschel, and G. Superti-Furga Regulation of the c-Abl and Bcr-Abl tyrosine kinases Nat Rev Mol Cell Biol 5 2004 33 44
35. O. Hantschel, S. Wiesner, T. Guttler, C.D. Mackereth, L.L. Rix, Z. Mikes, J. Dehne, D. Gorlich, M. Sattler, and G. Superti-Furga Structural basis for the cytoskeletal association of Bcr-Abl/c-Abl Mol Cell 19 2005 461 473
36. F. Michor, T.P. Hughes, Y. Iwasa, S. Branford, N.P. Shah, C.L. Sawyers, and M.A. Nowak Dynamics of chronic myeloid leukaemia Nature 435 2005 1267 1270 The decline of BCR-ABL transcript levels of chronic phase CML patients during the first year of imatinib therapy was analyzed using a quantitative model of disease dynamics. Under successful imatinib therapy, differentiated leukemic cells survive for ∼20 days, and more-primitive leukemic progenitors have a ∼sixfold longer lifespan. This model is consistent with the putative inability of imatinib to deplete leukemic stem cells.
37. K.J. Hope, L. Jin, and J.E. Dick Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity Nat Immunol 5 2004 738 743 Meticulous tracking of individual leukemic stem cells following serial transplantation of NOD-SCID (non-obese diabetic severe combined immunodeficient) mice with AML leukemia cells revealed that leukemic stem cells comprise a functionally heterogeneous class and exhibit a range of self-renewal capacities, in close analogy to normal hematopoietic stem cells.
38. M. Al-Hajj, M.W. Becker, M. Wicha, I. Weissman, and M.F. Clarke Therapeutic implications of cancer stem cells Curr Opin Genet Dev 14 2004 43 47
39. H.G. Jorgensen, E.K. Allan, S.M. Graham, J.L. Godden, L. Richmond, M.A. Elliott, J.C. Mountford, C.J. Eaves, and T.L. Holyoake Lonafarnib reduces the resistance of primitive quiescent CML cells to imatinib mesylate in vitro Leukemia 19 2005 1184 1191
40. J. Xiaoyan, Y. Zhao, W.Y. Chan, E. Pang, A. Eaves, and C. Eaves Leukemic stem cells of chronic phase CML patients consistently display very high BCR-ABL transcript levels and reduced responsiveness to imatinib mesylate in addition to generating a rare subset that produce imatinib mesylate resistant differentiated progeny Blood 104 2004 204a
41. R.S. Taichman Blood and bone: two tissues whose fates are intertwined to create the hematopoietic stem-cell niche Blood 105 2005 2631 2639
42. N.J. Donato, J.Y. Wu, J. Stapley, H. Lin, R. Arlinghaus, B. Aggarwal, S. Shishodin, M. Albitar, K. Hayes, and H. Kantarjian Imatinib mesylate resistance through BCR-ABL independence in chronic myelogenous leukemia Cancer Res 64 2004 672 677
43. J. Thomas, L. Wang, R.E. Clark, and M. Pirmohamed Active transport of imatinib into and out of cells: implications for drug resistance Blood 104 2004 3739 3745
44. J. Goldman Monitoring minimal residual disease in BCR-ABL-positive chronic myeloid leukemia in the imatinib era Curr Opin Hematol 12 2005 33 39
45. C.T. Jordan, and M.L. Guzman Mechanisms controlling pathogenesis and survival of leukemic stem cells Oncogene 23 2004 7178 7187
46. Z. Li, Y. Qiao, B. Liu, E.J. Laska, P. Chakravarthi, J.M. Kulko, R.D. Bona, M. Fang, U. Hegde, and V. Moyo Combination of imatinib mesylate with autologous leukocyte-derived heat shock protein and chronic myelogenous leukemia Clin Cancer Res 11 2005 4460 4468
47. J.A. Cancelas, A.W. Lee, R. Prabhakar, K.F. Stringer, Y. Zheng, and D.A. Williams Rac GTPases differentially integrate signals regulating hematopoietic stem cell localization Nat Med 11 2005 886 891
48. W. Eisterer, X. Jiang, O. Christ, H. Glimm, K.H. Lee, E. Pang, K. Lambie, G. Shaw, T.L. Holyoake, and A.L. Petzer Different subsets of primary chronic myeloid leukemia stem cells engraft immunodeficient mice and produce a model of the human disease Leukemia 19 2005 435 441
49. R. Trotta, T. Vignudelli, O. Candini, R.V. Intine, L. Pecorari, C. Guerzoni, G. Santilli, M.W. Byrom, S. Goldoni, and L.P. Ford BCR/ABL activates mdm2 mRNA translation via the La antigen Cancer Cell 3 2003 145 160
50. K. Kojima, M. Konopleva, I.J. Samudio, M. Shikami, M. Cabreira-Hansen, T. McQueen, V. Ruvolo, T. Tsao, Z. Zeng, and L.T. Vassilev MDM2 antagonists induce p53-dependent apoptosis in AML: implications for leukemia therapy Blood 106 2005 3150 3159
51. C.H. Jamieson, L.E. Ailles, S.J. Dylla, M. Muijtjens, C. Jones, J.L. Zehnder, J. Gotlib, K. Li, M.G. Manz, and A. Keating Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML N Engl J Med 351 2004 657 667 The authors suggest that progression to blast crisis might involve acquisition of self-renewal properties by committed progenitors. In this study, granulocyte-macrophage progenitors from patients with CML in blast crisis exhibited enhanced self-renewal activity and activation of β-catenin. These findings are intriguing but do not exclude the possibility that progression to blast crisis is initiated at the level of a more classic stem cell population.
52. A. Cozzio, E. Passegue, P.M. Ayton, H. Karsunky, M.L. Cleary, and I.L. Weissman Similar MLL-associated leukemias arising from self-renewing stem cells and short-lived myeloid progenitors Genes Dev 17 2003 3029 3035
53. B.J. Huntly, H. Shigematsu, K. Deguchi, B.H. Lee, S. Mizuno, N. Duclos, R. Rowan, S. Amaral, D. Curley, and I.R. Williams MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors Cancer Cell 6 2004 587 596
54. M. Talpaz, HM. Kantarjian, R. Paquette, N. Shah, J. Cortes, J. Nicoll, SA. Bai, F. Huang, AP. Decillis, and CL. Sawyers A phase I study of BMS-354825 in patients with imatinib-resistant and intolerant chronic phase chronic myeloid leukemia (CML): results from CA180002 Proc Am Soc Clin Oncol 23 2005 564s
55. CL. Sawyers, NP. Shah, HM. Kantarjian, J. Cortes, R. Paquette, J. Nicoll, SA. Bai, E. Clark, AP. Decillis, and M. Talpaz A phase I study of BMS-354825 in patients with imatinib-resistant and intolerant accelerated and blast phase chronic myeloid leukemia (CML): results from CA180002 Proc Am Soc Clin Oncol 23 2005 565s
56. H. Kantarjian, O. Ottmann, J. Cortes, B. Wassmann, D. Jones, A. Hochhaus, L. Alland, M. Dugan, M. Albitar, and F. Giles AMN107, a novel aminopyrimidine inhibitor of Bcr-Abl, has significant activity in imatinib-resistant bcr-abl positive chronic myeloid leukemia (CML) Proc Am Soc Clin Oncol 23 2005 195s
57. O. Ottmann, F. Giles, B. Wassmann, A. Hochhaus, P. Rae, M. Beran, M. Albitar, L. Alland, M. Dugan, and H. Kantarjian Activity of AMN107, a novel aminopyrimidine inhibitor of Bcr-Abl, in imatinib-resistant bcr-abl positive lymphoid malignancies Proc Am Soc Clin Oncol 23 2005 195s
58. 50 < 25 nm in each case). In vivo bone marrow transplantation assays demonstrated that AMN107 was an effective treatment for myeloproliferative disease induced by either TEL-PDGFRβ or FIP1L1-PDGFRα.