New insights into the pathogenesis of chronic myeloid leukaemia: Towards a path to cure

Netherlands Journal of Medicine

Volumn 69, Issue 10, 2011, Pages 430-440

  Thielen, N ^a   Ossenkoppele, G J ^a   Schuurhuis, G J ^a   Janssen, J J W M ^a  

^a VU UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

Chronic myeloid leukaemia; Leukaemic stem cells; Molecular pathways; Pathogenesis

Indexed keywords

BCR ABL PROTEIN; BETA CATENIN; BMI1 PROTEIN; BORTEZOMIB; GLYCOGEN SYNTHASE KINASE 3BETA; GROWTH ARREST SPECIFIC PROTEIN 6; IMATINIB; INTERFERON CONSENSUS SEQUENCE BINDING PROTEIN; INTERLEUKIN 3; JANUS KINASE; MYC PROTEIN; NOTCH RECEPTOR; ONCOPROTEIN; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PHOSPHOPROTEIN PHOSPHATASE 2A; PROMYELOCYTIC LEUKEMIA PROTEIN; STAT PROTEIN; TRANSCRIPTION FACTOR FKHRL1; TRANSCRIPTION FACTOR FOXO; WNT PROTEIN;

APOPTOSIS; BLAST CELL CRISIS; CHRONIC MYELOID LEUKEMIA; HEDGEHOG; HEMATOPOIETIC STEM CELL; HUMAN; MOUSE; NONHUMAN; PATHOGENESIS; PROTEIN BINDING; REVIEW;

DISEASE PROGRESSION; FUSION PROTEINS, BCR-ABL; GENES, ABL; HUMANS; LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE; PIPERAZINES; PROTEIN KINASE INHIBITORS; PROTEIN-TYROSINE KINASES; PYRIMIDINES; SIGNAL TRANSDUCTION;

EID: 80655139219     PISSN: 03002977     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (92)

1. Nowell PC, Hungerford DA. Chromosome studies on normal and leukemic human leukocytes. J Natl Cancer Inst. 1960;25:85-109.
2. Rowley JD. Identification of a translocation with quinacrine fluorescence in a patient with acute leukemia. Ann Genet. 1973;16:109-12.
3. Kavalerchik E, Goff D, Jamieson CH. Chronic myeloid leukemia stem cells. J Clin Oncol. 2008;26:2911-15.
4. Quintas-Cardama A, Cortes J. Molecular biology of bcr-abl1-positive chronic myeloid leukemia. Blood. 2009;113:1619-30.
5. Valent P. Emerging stem cell concepts for imatinib-resistant chronic myeloid leukaemia: implications for the biology, management, and therapy of the disease. Br J Haematol. 2008;142:361-78.
6. Drummond MW, Holyoake TL. Tyrosine kinase inhibitors in the treatment of chronic myeloid leukaemia: so far so good? Blood Rev. 2001;15:85-95.
7. Fialkow PJ, Jacobson RJ, Papayannopoulou T. Chronic myelocytic leukemia: clonal origin in a stem cell common to the granulocyte, erythrocyte, platelet and monocyte/macrophage. Am J Med. 1977;63:125-30.
8. Giralt S, Kantarjian H, Talpaz M. Treatment of chronic myelogenous leukemia. Semin Oncol. 1995;22:396-404.
9. Samanta AK, Chakraborty SN, Wang Y, et al. Destabilization of Bcr-Abl/ Jak2 Network by a Jak2/Abl Kinase Inhibitor ON044580 Overcomes Drug Resistance in Blast Crisis Chronic Myelogenous Leukemia (CML). Genes Cancer. 2010;1:346-59.
10. Daley GQ, Van Etten RA, Baltimore D. Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science. 1990;247:824-30.
11. Chalandon Y, Jiang X, Christ O, et al. BCR-ABL-transduced human cord blood cells produce abnormal populations in immunodeficient mice. Leukemia. 2005;19:442-8.
12. Haferlach T, Winkemann M, Nickenig C, et al. Which compartments are involved in Philadelphia-chromosome positive chronic myeloid leukaemia? An answer at the single cell level by combining May-Grunwald-Giemsa staining and fluorescence in situ hybridization techniques. Br J Haematol. 1997;97:99-106.
13. Takahashi N, Miura I, Saitoh K, Miura AB. Lineage involvement of stem cells bearing the Philadelphia chromosome in chronic myeloid leukemia in the chronic phase as shown by a combination of fluorescenceactivated cell sorting and fluorescence in situ hybridization. Blood. 1998;92:4758-63.
14. Bose S, Deininger M, Gora-Tybor J, Goldman JM, Melo JV. The presence of typical and atypical BCR-ABL fusion genes in leukocytes of normal individuals: biologic significance and implications for the assessment of minimal residual disease. Blood. 1998;92:3362-67.
15. Lukasova E, Kozubek S, Kozubek 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;100:525-35.
16. Misaghian N, Ligresti G, Steelman LS, et al. Targeting the leukemic stem cell: the Holy Grail of leukemia therapy. Leukemia. 2009;23:25-42.
17. Dameshek W. Some speculations on the myeloproliferative syndromes. Blood. 1951;6:372-5.
18. 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.
19. Daley GQ. Animal models of BCR/ABL-induced leukemias. Leuk Lymphoma. 1993;11 Suppl 1:57-60.
20. 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.
21. 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.
22. Jiang X, Saw KM, Eaves A, Eaves C. Instability of BCR-ABL gene in primary and cultured chronic myeloid leukemia stem cells. J Natl Cancer Inst. 2007;99:680-93.
23. Corbin AS, Agarwal A, Loriaux M, et al. Human chronic myeloid leukemia stem cells are insensitive to imatinib despite inhibition of BCR-ABL activity. J Clin Invest. 2011;121:396-409.
24. Jamieson CH. Chronic myeloid leukemia stem cells. Hematology Am Soc Hematol Educ Program. 2008;436-42.
25. Mahon FX, Rea D, Guilhot J, et al. Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol. 2010;11:1029-35.
26. Sutherland HJ, Lansdorp PM, Henkelman DH, Eaves AC, Eaves CJ. Functional characterization of individual human hematopoietic stem cells cultured at limiting dilution on supportive marrow stromal layers. Proc Natl Acad Sci USA. 1990;87:3584-8.
27. Eaves cJ, Cashman JD, Zoumbos NC, Barnett MJ, Eaves AC. Biological strategies for the selective manipulation of normal and leukemic stem cells. Stem Cells. 1993:11(Suppl 3):109-21.
28. Coulombel L, Kalousek DK, Eaves CJ, Gupta CM, Eaves AC. Long-term marrow culture reveals chromosomally normal hematopoietic progenitor cells in patients with Philadelphia chromosome-positive chronic myelogenous leukemia. N Engl J Med. 1983;308:1493-8.
29. Ponchio L, Conneally E, Eaves C. Quantitation of the quiescent fraction of long-term culture-initiating cells in normal human blood and marrow and the kinetics of their growth factor-stimulated entry into S-phase in vitro. Blood. 1995;86:3314-21.
30. Holyoake T, Jiang X, Eaves C, Eaves A. Isolation of a highly quiescent subpopulation of primitive leukemic cells in chronic myeloid leukemia. Blood. 1999;94:2056-64.
31. Holyoake TL, Jiang X, Jorgensen HG, et al. Primitive quiescent leukemic cells from patients with chronic myeloid leukemia spontaneously initiate factor-independent growth in vitro in association with up-regulation of expression of interleukin-3. Blood. 2001;97:720-8.
32. Eisterer W, Jiang X, Christ O, et al. Different subsets of primary chronic myeloid leukemia stem cells engraft immunodeficient mice and produce a model of the human disease. Leukemia. 2005;19:435-41.
33. Janssen JJ, Schuurhuis GJ, Terwijn M, Ossenkoppele GJ. Towards cure of CML: why we need to know more about CML stem cells? Curr Stem Cell Res Ther. 2009;4:224-36.
34. Danial NN, Rothman P. JAK-STAT signaling activated by Abl oncogenes. Oncogene. 2000;19:2523-31.
35. Xie S, Wang Y, Liu J, et al. Involvement of Jak2 tyrosine phosphorylation in Bcr-Abl transformation. Oncogene. 2001;20:6188-95.
36. Huang M, Dorsey JF, Epling-Burnette PK, et al. Inhibition of Bcr-Abl kinase activity by PD180970 blocks constitutive activation of Stat5 and growth of CML cells. Oncogene. 2002;21:8804-16.
37. Jatiani SS, Cosenza SC, Reddy MV, et al. A Non-ATP-Competitive Dual Inhibitor of JAK2 and BCR-ABL Kinases: Elucidation of a Novel Therapeutic Spectrum Based on Substrate Competitive Inhibition. Genes Cancer. 2010;1:331-45.
38. Samanta A, Perazzona B, Chakraborty S, et al. Janus kinase 2 regulates Bcr-Abl signaling in chronic myeloid leukemia. Leukemia. 2011;25:463-72.
39. Coluccia AM, Vacca A, Dunach M, et al. Bcr-Abl stabilizes beta-catenin in chronic myeloid leukemia through its tyrosine phosphorylation. EMBO J. 2007;26:1456-66.
40. Abrahamsson AE, Geron I, Gotlib J, et al. Glycogen synthase kinase 3beta missplicing contributes to leukemia stem cell generation. Proc Natl Acad Sci USA. 2009;106:3925-9.
41. Schmidt M, Hochhaus A, Nitsche A, Hehlmann R, Neubauer A. Expression of nuclear transcription factor interferon consensus sequence binding protein in chronic myeloid leukemia correlates with pretreatment brisk features and cytogenetic response to interferon-alpha. Blood. 2001;97:3648-50.
42. Huang W, Zhou W, Saberwal G, et al. Interferon consensus sequence binding protein (ICSBP) decreases beta-catenin activity in myeloid cells by repressing GAS2 transcription. Mol Cell Biol. 2010;30:4575-94.
43. Benetti R, Del SG, Monte M, et al. The death substrate Gas2 binds m-calpain and increases susceptibility to p53-dependent apoptosis. EMBO J. 2001;20:2702-14.
44. Neviani P, Santhanam R, Trotta R, et al. The tumor suppressor PP2A is functionally inactivated in blast crisis CML through the inhibitory activity of the BCR/ABL-regulated SET protein. Cancer Cell. 2005;8:355-68.
45. Neviani P, Santhanam R, Oaks JJ, et al. FTY720, a new alternative for treating blast crisis chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphocytic leukemia. J Clin Invest. 2007;117:2408-21.
46. Junttila MR, Puustinen P, Niemela M, et al. CIP2A inhibits PP2A in human malignancies. Cell. 2007;130:51-62.
47. Lucas CM, Harris RJ, Giannoudis A, et al. Cancerous inhibitor of PP2A (CIP2A) at diagnosis of chronic myeloid leukemia is a critical determinant of disease progression. Blood. 2011;117:6660-8.
48. Nakamura S, Yokota D, Tan L, et al. Down-regulation of Thanatosassociated protein 11 by BCR-ABL promotes CML cell proliferation through c-Myc expression. Int J Cancer. 2011 [Epub ahead of print]
49. Nilsson JA, Cleveland JL. Myc pathways provoking cell suicide and cancer. Oncogene. 2003;22:9007-21.
50. Kabarowski JH, Allen PB, Wiedemann LM. A temperature sensitive p210 BCR-ABL mutant defines the primary consequences of BCR-ABL tyrosine kinase expression in growth factor dependent cells. EMBO J. 1994;13:5887-95.
51. Samanta AK, Lin H, Sun T, Kantarjian H, Arlinghaus RB. Janus kinase 2: a critical target in chronic myelogenous leukemia. Cancer Res. 2006;66:6468-72.
52. Gesbert F, Griffin JD. Bcr/Abl activates transcription of the Bcl-X gene through STAT5. Blood. 2000;96:2269-76.
53. Kuribara R, Honda H, Matsui H, et al. Roles of Bim in apoptosis of normal and Bcr-Abl-expressing hematopoietic progenitors. Mol Cell Biol. 2004;24:6172-83.
54. Chang F, Lee JT, Navolanic PM, et al. Involvement of PI3K/Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation: a target for cancer chemotherapy. Leukemia. 2003;17:590-603.
55. Horita M, Andreu EJ, Benito A, et al. Blockade of the Bcr-Abl kinase activity induces apoptosis of chronic myelogenous leukemia cells by suppressing signal transducer and activator of transcription 5-dependent expression of Bcl-xL. J Exp Med. 2000;191:977-84.
56. Aichberger KJ, Mayerhofer M, Krauth MT, et al. Low-level expression of proapoptotic Bcl-2-interacting mediator in leukemic cells in patients with chronic myeloid leukemia: role of BCR/ABL, characterization of underlying signaling pathways, and reexpression by novel pharmacologic compounds. Cancer Res. 2005;65:9436-44.
57. Kuzelova K, Pluskalova M, Grebenova D, et al. Changes in cell adhesivity and cytoskeleton-related proteins during imatinib-induced apoptosis of leukemic JURL-MK1 cells. J Cell Biochem. 2010;111:1413-25.
58. Jongen-Lavrencic M, Salesse S, Delwel R, Verfaillie CM. BCR/ ABL-mediated downregulation of genes implicated in cell adhesion and motility leads to impaired migration toward CCR7 ligands CCL19 and CCL21 in primary BCR/ABL-positive cells. Leukemia. 2005;19:373-80.
59. Salgia R, Sattler M, Pisick E, Li JL, Griffin JD. p210BCR/ABL induces formation of complexes containing focal adhesion proteins and the protooncogene product p120c-Cbl. Exp Hematol. 1996;24:310-3.
60. Walker JL, Fournier AK, Assoian RK. Regulation of growth factor signaling and cell cycle progression by cell adhesion and adhesion-dependent changes in cellular tension. Cytokine Growth Factor Rev. 2005;16:395-405.
61. Bhatia R, Munthe HA, Verfaillie CM. Role of abnormal integrincytoskeletal interactions in impaired beta1 integrin function in chronic myelogenous leukemia hematopoietic progenitors. Exp Hematol. 1999;27:1384-96.
62. Jiang Y, Prosper F, Verfaillie CM. Opposing effects of engagement of integrins and stimulation of cytokine receptors on cell cycle progression of normal human hematopoietic progenitors. Blood. 2000;95:846-54.
63. Long B, Zhu H, Zhu C, Liu T, Meng W. Activation of the Hedgehog pathway in chronic myelogeneous leukemia patients. J Exp Clin Cancer Res. 2011;30:8.
64. Zhao C, Chen A, Jamieson CH, et al. Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia. Nature. 2009;458:776-9.
65. Chen Y, Peng C, Sullivan C, Li D, Li S. Critical molecular pathways in cancer stem cells of chronic myeloid leukemia. Leukemia. 2010;24:1545-54.
66. Trowbridge JJ, Xenocostas A, Moon RT, Bhatia M. Glycogen synthase kinase-3 is an in vivo regulator of hematopoietic stem cell repopulation. Nat Med. 2006;12:89-98.
67. Dierks C, Beigi R, Guo GR, et al. Expansion of Bcr-Abl-positive leukemic stem cells is dependent on Hedgehog pathway activation. Cancer Cell. 2008;14:238-49.
68. Mohty M, Yong AS, Szydlo RM, Apperley JF, Melo JV. The polycomb group BMI1 gene is a molecular marker for predicting prognosis of chronic myeloid leukemia. Blood. 2007;110:380-3.
69. Yong AS, Stephens N, Weber G, et al. Improved outcome following allogeneic stem cell transplantation in chronic myeloid leukemia is associated with higher expression of BMI-1 and immune responses to BMI-1 protein. Leukemia 2011;25:629-37.
70. Mohty M, Szydlo RM, Yong AS, et al. Association between BMI-1 expression, acute graft-versus-host disease, and outcome following allogeneic stem cell transplantation from HLA-identical siblings in chronic myeloid leukemia. Blood. 2008;112:2163-6.
71. Yin DD, Fan FY, Hu XB, et al. Notch signaling inhibits the growth of the human chronic myeloid leukemia cell line K562. Leuk Res. 2009;33:109-14.
72. Mizuno T, Yamasaki N, Miyazaki K, et al. Overexpression/enhanced kinase activity of BCR/ABL and altered expression of Notch1 induced acute leukemia in p210BCR/ABL transgenic mice. Oncogene. 2008;27:3465-74.
73. Ito K, Bernardi R, Morotti A, et al. PML targeting eradicates quiescent leukaemia-initiating cells. Nature. 2008;453:1072-8.
74. Bruns I, Czibere A, Fischer JC, et al. The hematopoietic stem cell in chronic phase CML is characterized by a transcriptional profile resembling normal myeloid progenitor cells and reflecting loss of quiescence. Leukemia. 2009;23:892-9.
75. Covey TM, Edes K, Fitzpatrick FA. Akt activation by arachidonic acid metabolism occurs via oxidation and inactivation of PTEN tumor suppressor. Oncogene. 2007;26:5784-92.
76. Peng C, Chen Y, Yang Z, et al. PTEN is a tumor suppressor in CML stem cells and BCR-ABL-induced leukemias in mice. Blood. 2010;115:626-35.
77. Chen Y, Hu Y, Zhang H, Peng C, Li S. Loss of the Alox5 gene impairs leukemia stem cells and prevents chronic myeloid leukemia. Nat Genet. 2009;41:783-92.
78. Roos C, Stenke L, Ohm L, et al. Clinical imatinib mesylate treatment induces early normalisation of aberrant neutrophil leukotriene C4 synthase expression and activity in chronic myeloid leukaemia. Br J Haematol. 2008;142:992-5.
79. Chen Y, Li D, Li S. The Alox5 gene is a novel therapeutic target in cancer stem cells of chronic myeloid leukemia. Cell Cycle. 2009;8:3488-92.
80. Tothova Z, Kollipara R, Huntly BJ, et al. FoxOs are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress. Cell. 2007;128:325-39.
81. Naka K, Hoshii T, Hirao A. Novel therapeutic approach to eradicate tyrosine kinase inhibitor resistant chronic myeloid leukemia stem cells. Cancer Sci. 2010;101:1577-81.
82. Naka K, Hoshii T, Muraguchi T, et al. TGF-beta-FOXO signaling maintains leukaemia-initiating cells in chronic myeloid leukaemia. Nature. 2010;463:676-80.
83. Dewar R, Chen ST, Yeckes-Rodin H, Miller K, Khosravi-Far R. Bortezomib treatment causes remission in a Ph+ALL patient and reveals FoxO as a theranostic marker. Cancer Biol Ther. 2011;11:552-8.
84. Deininger M, O'Brien SG, Guilhot F, et al. International randomized study of interferon vs STI571 (IRIS) 8-year follow up: Sustained survival and low risk for progression or events in patients with newly diagnosed chronic myeloid leukemia chronic phase (CML-CP) treated with imatinib. Blood. 114, 2009 (abstract 1126).
85. Perrotti D, Jamieson C, Goldman J, Skorski T. Chronic myeloid leukemia: mechanisms of blastic transformation. J Clin Invest. 2010;120:2254-64.
86. Brassat U, Balabanov S, Bali D, et al. Functional p53 is required for effective execution of telomerase inhibition in BCR-ABL-positive CML cells. Exp Hematol. 2011;39:66-76.
87. Roman-Gomez J, Jimenez-Velasco A, Agirre X, et al. Repetitive DNA hypomethylation in the advanced phase of chronic myeloid leukemia. Leuk Res. 2008;32:487-90.
88. Janssen JJ, Denkers F, Valk P, et al. Methylation patterns in CD34 positive chronic myeloid leukemia blast crisis cells. Haematologica. 2010;95:1036-7.
89. Koptyra M, Falinski R, Nowicki MO, et al. BCR/ABL kinase induces self-mutagenesis via reactive oxygen species to encode imatinib resistance. Blood. 2006;108:319-27.
90. Sallmyr A, Tomkinson AE, Rassool FV. Up-regulation of WRN and DNA ligase IIIalpha in chronic myeloid leukemia: consequences for the repair of DNA double-strand breaks. Blood. 2008;112:1413-23.
91. Ito T, Kwon HY, Zimdahl B, et al. Regulation of myeloid leukaemia by the cell-fate determinant Musashi. Nature. 2010;466:765-8.
92. Preudhomme C, Guilhot J, Nicolini FE, et al. Imatinib plus peginterferon alfa-2a in chronic myeloid leukemia. N Engl J Med. 2010;363:2511-21.