Best Practice & Research Clinical Haematology
Volume 22, Issue 3 , Pages 285-294 , September 2009

CML: a model for targeted therapy

  • Daniela Cilloni, MD (Doctor)
    • ,
  • Giuseppe Saglio, MD (Professor)

      Affiliations

    • Corresponding Author InformationCorresponding author. S. Luigi Hospital, Regione Gonzole 10, 10043, Orbassano Turin, Italy. Tel.: +390113576056; Fax: +390119038636.

References 

  1. Nowell PC, Hungerford DA. A minute chromosome in human chronic granulocytic leukemia. Science. 1960;32:1497–1501
  2. Groffen J, Stephenson JR, Heisterkamp N, et al. Philadelphia chromosome breakpoint are clustered within a limited region, bcr, on chromosome 22. Cell. 1984;33:93–99
  3. Daley GQ, Van Etten RA, Baltimore D. Induction of chronic myelogenous leukemia in mice by 210 bcr-abl gene of the Philadelphia chromosome. Science. 1990;87:6649–6653
  4. Elefanty AG, Hariharan IK, Cory S. Bcr-Abl, the hallmark of chronic myeloid leukaemia in man, induces multiple haemopoietic neoplasms in mice. EMBO J. 1990;9:1069–1078
  5. Kelliher MA, McLaughlin J, Witte ON, et al. Induction of a chronic myelogenous leukemia-like syndrome in mice with v-abl and BCR/ABL. Proc Natl Acad Sci U S A. 1990;87:6649–6653
  6. Pear WS, Miller JP, Xu L, et al. Efficient and rapid induction of a chronic myelogenous leukemia-like disease in mice receiving p210bcr-abl-transformed bone marrow. Blood. 1998;92:3780–3792
  7. Heisterkamp N, Jenster G, ten Hoeve J. Acute leukaemia in bcr/abl transgenic mice. Nature. 1990;344:251–253
  8. Ben-Neriah Y, Daley GQ, Mes-Masson A, et al. The chronic myelogenous leukemia-specific p210 protein is the product of the bcr-abl hybrid gene. Science. 1986;233:212–214
  9. Goldman JM, Melo JV. Chronic myeloid leukemia–advances in biology and new approaches to treatment. N Engl J Med. 2003;349:1451–1464
  10. Melo JV. The diversity of Bcr-Abl fusion proteins and their relationship to leukemia phenotype. Blood. 1996;88:2375–2384
  11. Buchdunger E, Zimmermann J, Mett H, et al. Inhibition of the Abl protein-tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative. Cancer Res. 1996;56:100–104
  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;2:561–566
  13. Konopka JB, Watanabe SM, Witte ON. An alteration of the human c-abl protein in K562 leukemia cells unmasks associated tyrosine kinase activity. Cell. 1984;37:1035–1042
  14. Lugo TG, Pendergast AM, Muller AJ, et al. Tyrosine kinase activity and transformation potency of bcr-abl oncogene products. Science. 1990;247:1079–1082
  15. Lukasova E, Kozubek S, Kosubek M, et al. Localisation and distance between ABL and BCR genes in interphase nuclei of bone marrow cells of control donors and patients with chronic myeloid leukaemia. Hum Genet. 1997;100:525–535
  16. Neves H, Ramos C, da Sila MG, et al. The nuclear topography of ABL, BCR, PML and RAR genes: evidence for gene proximity in specific phases of the cell cycle and stages of hematopoietic differentiation. Blood. 1999;93:1197–1207
  17. Saglio G, Storlazzi CT, Giugliano E, et al. A 76-kb duplicon maps close to the BCR gene on chromosome 22 and the ABL gene on chromosome 9: possible involvement in the genesis of Philadelphia chromosome. Proc Natl Acad Sci U S A. 2002;99:9882–9887
  18. Pawarode A, Sait SNJ, Nganga A, et al. Acute myeloid leukaemia developing during imatinib mesylate therapy for chronic myeloid leukemia in the absence of new cytogenetic abnormalities. Leuk Res. 2007;31:1589–1592
  19. Fialkow PJ, Martin PJ, Najfeld V, et al. Evidence for a multistep pathogenesis of chronic myelogenous leukemia. Blood. 1981;58:158–163
  20. Raskind WH, Ferraris AM, Najfeld V, et al. Further evidence for the existence of a clonal Ph-negative stage in some cases of Ph-positive chronic myelocytic leukemia. Leukemia. 1993;7:1163–1167
  21. Biernaux C, Loos M, Sels A, et al. Detection of major bcr-abl gene expression at a very low level in blood cells of some healthy individuals. Blood. 1995;86:3118–3122
  22. O'Dwyer ME, Gatter KM, Loriaux M, et al. Demonstration of Philadelphia chromosome negative abnormal clones in patients with chronic myelogenous leukemia during major cytogenetic responses induced by imatinib mesylate. Leukemia. 2003;17:481–487
  23. Bumm T, Muller C, Al Ali HK, et al. Emergence of clonal cytogenetic abnormalities in Ph-cells in some CML patients in cytogenetic remission to imatinib but restoration of polyclonal hematopoiesis in the majority. Blood. 2003;101:1941–1949
  24. Radich JP, Dai H, Mao M, et al. Gene expression changes associated with progression and response in chronic myeloid leukemia. Proc Natl Acad Sci U S A. 2006;103:2794–2799
  25. Zheng C, Li L, Haak M, et al. Gene expression profiling of CD34+ cells identifies a molecular signature of chronic myeloid leukemia blast crisis. Leukemia. 2006;20:1028–1034
  26. Pendergast AM, Muller AJ, Havlik MH, et al. BCR sequences essential for transformation by the BCR-ABL oncogene bind to the ABL SH2 regulatory domain in a non-phosphotyrosine-dependent manner. Cell. 1991;66:161–171
  27. Pendergast AM, Quilliam LA, Cripe LD, et al. BCR-ABL-induced oncogenesis is mediated by direct interaction with the SH2 domain of the GRB-2 adaptor protein. Cell. 1993;75:175–185
  28. Melo JV, Deininger MWN. Biology of chronic myelogenous leukemia – signaling pathways of initiation and transformation. Hematol Oncol Clin North Am. 2004;118:545–568
  29. Cortez D, Reuther GW, Pendergast AM. The BCR-ABL tyrosine kinase activates mitotic signaling pathways and stimulates G1-to-S phase transition in hematopoietic cells. Oncogene. 1997;15:2333–2342
  30. Pelicci G, Lanfrancone L, Salcini AE, et al. Constitutive phosphorylation of Shc proteins in human tumors. Oncogene. 1995;11:899–907
  31. Sattler M, Salgia R, Okuda K, et al. The proto-oncogene product p120CBL and the adaptor proteins CRKL and c-CRK link c-ABL, p190BCR/ABL and p210BCR/ABL to the phosphatidylinositol–3 ¢ kinase pathway. Oncogene. 1996;12:839–846
  32. 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 U S A. 1995;92:11746–11750
  33. Sawyers CL, McLaughlin J, Witte ON. Genetic requirement for RAS in the trasformation of fibroblasts and hematopoietic cells by the BCR-ABL oncogene. J Exp Med. 1995;181:307–313
  34. Ilaria RL, Van Etten RA. P210 and P190(BCR/ABL) induce the tyrosine phosphorylation and DNA binding activity of multiple specific STAT family members. J Biol Chem. 1996;271:31704–31710
  35. Carlesso N, Frank DA, Griffin JD. Tyrosyl phosphorylation and DNA binding activity of signal transducers and activators of transcription (STAT) proteins in hematopoietic cell lines transformed by Bcr/Abl. J Exp Med. 1996;183:811–820
  36. Varticovski L, Daley GQ, Jackson P, et al. Activation of phosphatidylinositol 3-kinase in cells expressing abl oncogene variants. Mol Cell Biol. 1991;11:1107–1113
  37. Kauffmann-Zeh A, Rodriguez-Viciana P, Ulrich E, et al. Suppression of c-Myc induced apoptosis by Ras signalling through PI 3-kinase and PKB. Nature. 1997;385:544–548
  38. Sattler M, Mohi MG, Pride YB, et al. Critical role for Gab2 in transformation by BCR/ABL. Cancer Cell. 2002;1:479–492
  39. Skorski T, Bellacosa A, Nieborowska-Skorska M, et al. Transformation of hematopoietic cells by BCR/ABL requires activation of a PI–3k/Akt-dependent pathway. EMBO J. 1997;16:6151–6161
  40. Jain SK, Susa M, Keeler ML, et al. PI 3-kinase activation in BCR/abl-transformed hematopoietic cells does not require interaction of p85 SH2 domains with p210 BCR/abl. Blood. 1996;88:1542–1550
  41. Franke TF, Kaplan DR, Cantley LC. PI3K: downstream AKT blocks apoptosis. Cell. 1997;88:435–437
  42. Sawyers CL, Callahan W, Witte ON. Dominant negative MYC blocks transformation by ABl oncogenes. Cell. 1992;70:901–910
  43. Xie S, Lin H, Sun T, et al. Jak2 is involved in c-Myc induction by Bcr-Abl. Oncogene. 2002;17:7137–7146
  44. Bhatia R, McGlave PB, Dewald GW, et al. Abnormal function of the bone marrow microenvironment in chronic myelogenous leukemia: role of malignant stromal macrophages. Blood. 1995;85:3636–3645
  45. Upadhyaya G, Guba SC, Sih SA, et al. Interferon-alpha restores the deficient expression of the cytoadhesion molecule lymphocyte function antigen-3 by chronic myelogenous leukaemia progenitor cells. J Clin Invest. 1991;88:2131–2136
  46. Gordon MY, Dowding CR, Riley GP, et al. Altered adhesive interactions with marrow stroma of haemopoietic progenitor cells in chronic myeloid leukemia. Nature. 1987;328:342–344
  47. 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;111:2843–2853
  48. Uematsu K, He B, You L, et al. Activation of the Wnt pathway in non small cell lung cancer: evidence of dishevelled overexpression. Oncogene. 2003;22:7218–7221
  49. 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;351:657–667
  50. Perrotti D, Cesi V, Trotta R, et al. BCR-ABL suppresses C/EBPalpha expression through inhibitory action of hnRNP E2. Nat Genet. 2002;30:48–58
  51. Carroll M, Ohno-Jones S, Tamura S, et al. CGP 57148, a tyrosine kinase inhibitor, inhibits the growth of cells expressing BCR-ABL, TEL-ABL, and TEL-PDGFR fusion proteins. Blood. 1997;90:4947–4952
  52. Heinrich MC, Griffith DJ, Druker BJ, et al. Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor. Blood. 2000;96:925–932
  53. Deininger M, Buchdunger E, Druker BJ. The development of imatinib as a therapeutic agent for chronic myeloid leukemia. Blood. 2005;105:2640–2653
  54. Druker BJ, Talpaz M, Resta D, et al. Efficacy and safety of a specific inhibitor of the Bcr-Abl tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 2001;344:1031–1037
  55. 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 leukaemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med. 2001;344:1038–1042
  56. Kantarjian H, Sawyers C, Hochhaus A, et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med. 2002;346:645–652
  57. Hochhaus A, Druker B, Sawyers C, et al. Favorable long-term follow-up results over 6 years for response, survival, and safety with imatinib mesylate therapy in chronic-phase chronic myeloid leukaemia after failure of interferon-alpha treatment. Blood. 2008;111:1039–1043
  58. Sawyers CL, Hochhaus A, Feldman E, et al. Imatinib induces hematologic and cytogenetic responses in patients with chronic myeloid leukaemia in myeloid blast crisis: results of a phase II study. Blood. 2002;99:3530–3539
  59. Talpaz M, Silver RT, Druker BJ, 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
  60. 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. 13 Mar 2003;348:994–1004
  61. Druker BJ, Guilhot F, O'Brien SG, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355:2408–2417
  62. 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;293:876–880
  63. Corbin AS, Buchdunger E, Pascal F, et al. Analysis of the structural basis of specificity of inhibition of the Abl kinase by STI571. J Biol Chem. 2002;277:32214–32219
  64. Shah NP, Nicoll JM, Nagar B, et al. Multiple BCRABL 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
  65. Apperley JF. Mechanisms of resistance to imatinib in chronic myeloid leukaemia. Lancet Oncol. 2007;8:1018–1029
  66. Cortes , O'Dwyer ME. Clonal evolution in chronic myelogenous leukaemia. Hematol Oncol Clin North Am. 2004;18:671–684
  67. Kreil S, Pfirrmann M, Haferlach C, et al. German Chronic Myelogenous Leukemia (CML) Study Group. Heterogeneous prognostic impact of derivative chromosome 9 deletions in chronic myelogenous leukemia. Blood. 2007;110:1283–1290
  68. Deutsch , Dugray , AbdulKarim , et al. BCR-ABL down-regulates the DNA repair protein DNA-PKcs. Blood. 2001;97:2084–2090
  69. Janssen SM, Klaver Q, Waisfisz G, et al. Identification of genes potentially involved in disease transformation of CML. Leukemia. 2005;19:998–1004
  70. Johansson B, Fioretos T, Mitelman F. Cytogenetic and molecular genetic evolution of chronic myeloid leukaemia. Acta Haematol. 2002;107:76–94
  71. Weisberg E, Manley PW, Breitenstein W, et al. Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl. Cancer Cell. 2005;7:129–141
  72. Lombardo LJ, Lee FY, Chen P, 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
  73. Shah NP, Tran C, Lee FY, et al. Overriding imatinib resistance with a novel ABL kinase inhibitor. Science. 2004;305:399–401
  74. Hochhaus A, Kantarjian HM, Baccarani M, 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
  75. Kantarjian H, Giles F, Wunderle L, et al. Nilotinib in imatinib-resistant CML and Philadelphia chromosome- positive ALL. N Engl J Med. 2006;354:2542–2551
  76. Kantarjian HM, Giles F, Gattermann N, et al. Nilotinib (formerly AMN107), a highly selective BCRABL tyrosine kinase inhibitor, is effective in patients chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance. Blood. 2007;110:3540–3546
  77. O'Hare T, Eide CA, Tyner JW, et al. SGX393 inhibits the CML mutant Bcr-AblT315I and preempts in vitro resistance when combined with nilotinib or dasatinib. Proc Natl Acad Sci U S A. 2008;105:5507–5512
  78. Elrick LJ, Jorgensen HG, Mountford JC, et al. Punish the parent not the progeny. Blood. 2005;105:1862–1866

PII: S1521-6926(09)00022-X

doi: 10.1016/j.beha.2009.04.004

Best Practice & Research Clinical Haematology
Volume 22, Issue 3 , Pages 285-294 , September 2009

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