Biology of chronic myelogenous leukemia - Signaling pathways of initiation and transformation

Hematology/Oncology Clinics of North America

Volumn 18, Issue 3, 2004, Pages 545-568

  Melo, Junia V ^a   Deininger, Michael W N ^b  

^a HAMMERSMITH HOSPITAL   (United Kingdom)

^b OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BCR ABL PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE; PROTEASOME; PROTEIN DERIVATIVE; PROTEIN TYROSINE KINASE;

APOPTOSIS; BIOLISTIC TRANSFORMATION; CANCER RISK; CARBOXY TERMINAL SEQUENCE; CHROMOSOME 11; CHROMOSOME 22; CHROMOSOME 9; CHRONIC MYELOID LEUKEMIA; ENZYME ACTIVATION; EXON; GENE CLUSTER; GENE FUNCTION; GENE FUSION; GENETIC CODE; GENETIC TRANSCRIPTION; GENETIC TRANSFECTION; HUMAN; MOLECULAR BIOLOGY; MOLECULAR MECHANICS; ONCOGENE; ONCOGENE RAS; PHENOTYPE; PRIORITY JOURNAL; PROTEIN DEGRADATION; RECIPROCAL CHROMOSOME TRANSLOCATION; REVIEW; SIGNAL TRANSDUCTION; STATISTICAL SIGNIFICANCE;

CELL TRANSFORMATION, NEOPLASTIC; FUSION PROTEINS, BCR-ABL; HUMANS; LEUKEMIA, MYELOID, CHRONIC; ONCOGENE PROTEINS; SIGNAL TRANSDUCTION; TRANSLOCATION, GENETIC;

EID: 3242804413     PISSN: 08898588     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.hoc.2004.03.008     Document Type: Review

References (162)

1. Surralles J, Puerto S, Ramirez MJ, Creus A, Marcos R, Mullenders LH, et al. Links between chromatin structure, DNA repair and chromosome fragility. Mutat Res 1998;404(1-2):39-44.
2. Tanaka K, Takechi M, Hong J, Shigeta C, Oguma N, Kamada N, et al. 9;22 translocation and bcr rearrangements in chronic myelocytic leukemia patients among atomic bomb survivors. J Radiat Res (Tokyo) 1989;30(4):352-8.
3. Corso A, Lazzarino M, Morra E, Merante S, Astori C, Bernasconi P, et al. Chronic myelogenous leukemia and exposure to ionizing radiation - a retrospective study of 443 patients. Ann Hematol 1995;70(2):79-82.
4. Deininger MW, Bose S, Gora TJ, Yan XH, Goldman JM, Melo JV. Selective induction of leukemia-associated fusion genes by high-dose ionizing radiation. Cancer Res 1998;58(3):421-5.
5. Kozubek S, Lukasova E, Ryznar L, Kozubek M, Liskova A, Govorun RD, et al. Distribution of ABL and BCR genes in cell nuclei of normal and irradiated lymphocytes. Blood 1997;89(12):4537-45.
6. Neves H, Ramos C, da Silva MG, Parreira A, Parreira L. The nuclear topography of ABL, BCR, PML, and RARalpha genes: evidence for gene proximity in specific phases of the cell cycle and stages of hematopoietic differentiation [comments]. Blood 1999;93(4):1197-207.
7. Anastasi J, Moinuddin R, Daugherty C. The juxtaposition of ABL with BCR and risk for fusion may come at the time of BCR replication in late S-phase. Blood 1999;94(3):1137-8.
8. Chissoe SL, Bodenteich A, Wang YF, Wang YP, Burian D, Clifton SW, et al. Sequence and analysis of the human ABL gene, the BCR gene, and regions involved in the Philadelphia chromosomal translocation. Genomics 1995;27(1):67-82.
9. Saglio G, Storlazzi CT, Giugliano E, Surace C, Anelli L, Rege-Cambrin G, 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 the Philadelphia chromosome translocation. Proc Natl Acad Sci USA 2002;99(15):9882-7.
10. Sinclair PB, Nacheva EP, Leversha M, Telford N, Chang J, Reid A, et al. Large deletions at the t(9;22) breakpoint are common and may identify a poor-prognosis subgroup of patients with chronic myeloid leukemia. Blood 2000;95(3):738-43.
11. Huntly BJ, Reid AG, Bench AJ, Campbell LJ, Telford N, Shepherd P, et al. Deletions of the derivative chromosome 9 occur at the time of the Philadelphia translocation and provide a powerful and independent prognostic indicator in chronic myeloid leukemia. Blood 2001;98(6):1732-8.
12. Huntly BJ, Guilhot F, Reid AG, Vassiliou G, Hennig E, Franke C, et al. Imatinib improves but may not fully reverse the poor prognosis of patients with CML with derivative chromosome 9 deletions. Blood 2003;102(6):2205-12.
13. Kolomietz E, Marrano P, Yee K, Thai B, Braude I, Kolomietz A, et al. Quantitative PCR identifies a minimal deleted region of 120 kb extending from the Philadelphia chromosome ABL translocation breakpoint in chronic myeloid leukemia with poor outcome. Leukemia 2003;17(7):1313-23.
14. Melo JV. The diversity of BCR-ABL fusion proteins and their relationship to leukemia phenotype [editorial]. Blood 1996;88(7):2375-84.
15. Ravandi F, Cortes J, AlBitar M, Arlinghaus R, Qiang GJ, Talpaz M, et al. Chronic myelogenous leukaemia with p185(BCR/ABL) expression: characteristics and clinical significance. Br J Haematol 1999;107(3):581-6.
16. Dhingra K, Talpaz M, Kantarjian H, Ku S, Rothberg J, Gutterman JU, et al. Appearance of acute leukemia-associated P190BCR-ABL in chronic myelogenous leukemia may correlate with disease progression. Leukemia 1991;5(3):191-5.
17. Saglio G, Pane F, Gottardi E, Frigeri F, Buonaiuto MR, Guerrasio A, et al. Consistent amounts of acute leukemia-associated P190BCR/ABL transcripts are expressed by chronic myelogenous leukemia patients at diagnosis. Blood 1996;87(3):1075-80.
18. van Rhee F, Hochhaus A, Lin F, Melo JV, Goldman JM, Cross NCP, et al. p190 BCR-ABL mRNA is expressed at low levels in p210-positive chronic myeloid and acute lymphoblastic leukemias. Blood 1996;87(12):5213-7.
19. Lichty BD, Keating A, Callum J, Yee K, Croxford R, Corpus G, et al. Expression of p210 and p190 BCR-ABL due to alternative splicing in chronic myelogenous leukaemia. Br J Haematol 1998;103(3):711-5.
20. Pane F, Frigeri F, Sindona M, Luciano L, Ferrara F, Cimino R, et al. Neutrophilic-chronic myeloid leukemia (CML-N): a distinct disease with a specific molecular marker (BCR/ABL with C3/A2 junction) [comments]. Blood 1996;88(7):2410-4.
21. Hochhaus A, Reiter A, Skladny H, Melo JV, Sick C, Berger U, et al. A novel BCR-ABL fusion gene (e6a2) in a patient with Philadelphia chromosome negative chronic myelogenous leukemia. Blood 1996;88(6):2236-40.
22. Dupont M, Jourdan E, Chiesa J. Identification of E6A2 BCR-ABL fusion in a Philadelphiapositive CML. Leukemia 2000;14(11):2011-2.
23. Schultheis B, Wang L, Clark RE, Melo JV. BCR-ABL with an e6a2 fusion in a CML patient diagnosed in blast crisis. Leukemia 2003;17(10):2054-5.
24. Leibundgut EO, Jotterand M, Rigamonti V, Parlier V, Muhlematter D, Tobler A, et al. A novel BCR-ABL transcript e2a2 in a chronic myelogenous leukaemia patient with a duplicated Ph-chromosome and monosomy 7. Br J Haematol 1999;106(4):1041-4.
25. How GF, Lim LC, Kulkarni S, Tan LT, Tan P, Cross NC. Two patients with novel BCR/ABL fusion transcripts (e8/a2 and e13/a2) resulting from translocation breakpoints within BCR exons. Br J Haematol 1999;105(2):434-6.
26. Moreno MP, Cortinas MN, Bonomi R, Cardeza A, Uriarte MR. A novel BCR-ABL fusion transcript (e15a2) in 2 patients with atypical chronic myeloproliferative syndrome. Blood 2001;97(11):3668-9.
27. Byrne JL, Carter GI, Davies JM, Haynes AP, Russell NH, Cross NC. A novel BCR-ABL fusion gene (e2/1a) in a patient with Philadelphia- positive chronic myelogenous leukaemia and an aggressive clinical course. Br J Haematol 1998;103(3):791-4.
28. Soekarman D, van Denderen J, Hoefsloot L, Moret M, Meeuwsen T, van Baal J, et al. A novel variant of the bcr-abl fusion product in Philadelphia chromosome-positive acute lymphoblastic leukemia [comments]. Leukemia 1990;4(6):397-403.
29. Wilson GA, Vandenberghe EA, Pollitt RC, Rees DC, Goodeve AC, Peake IR, et al. Are aberrant BCR-ABL transcripts more common than previously thought? Br J Haematol 2000;111(4):1109-11.
30. Al-Ali HK, Leiblein S, Kovacs I, Hennig E, Niederwieser D, Deininger MWN. CML with an e1a3 BCR-ABL fusion: rare, benign, and a potential diagnostic pitfall. Blood 2002;100(3):1092-3.
31. Inukai T, Sugita K, Suzuki T, Ijima K, Goi K, Tezuka T, et al. A novel 203 kD aberrant BCRABL product in a girl with Philadelphia chromosome positive acute lymphoblastic leukaemia. Br J Haematol 1993;85(4):823-5.
32. Shiratsuchi M, Muta K, Minami R, Motomura S, Suehiro Y, Abe Y, et al. Aberrant BCR-ABL transcript with intronic insertion in a patient with Philadelphia chromosome-positive chronic myeloid leukemia: implications for disease progression. Leuk Lymphoma 2001;41(3-4):411-5.
33. Roman J, Parziale A, Gottardi E, de Micheli D, Cilloni D, Tiribelli M, et al. Novel type of BCR-ABL transcript in a chronic myelogenous leukaemia patient relapsed after bone marrow transplantation. Br J Haematol 2000;111(2):644-6.
34. Biernaux C, Loos M, Sels A, Huez G, Stryckmans P. Detection of major bcr-abl gene expression at a very low level in blood cells of some healthy individuals. Blood 1995;86(8):3118-22.
35. Bose S, Deininger M, Gora TJ, 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(9):3362-7.
36. Laurent E, Talpaz M, Kantarjian H, Kurzrock R. The BCR gene and Philadelphia chromosomepositive leukemogenesis. Cancer Res 2001;61(6):2343-55.
37. Maru Y, Witte ON. The BCR gene encodes a novel serine/threonine kinase activity within a single exon. Cell 1991;67(3):459-68.
38. Reuther GW, Fu H, Cripe LD, Collier RJ, Pendergast AM. Association of the protein kinases c-Bcr and Bcr-Abl with proteins of the 14-3-3 family [comments]. Science 1994;266(5182):129-33.
39. Pendergast AM, Quilliam LA, Cripe LD, Bassing CH, Dai Z, Li N, et al. BCR-ABL-induced oncogenesis is mediated by direct interaction with the SH2 domain of the GRB-2 adaptor protein. Cell 1993;75(1):175-85.
40. Pendergast AM, Muller AJ, Havlik MH, Maru Y, Witte ON. 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(1):161-71.
41. He Y, Wertheim JA, Xu L, Miller JP, Karnell FG, Choi JK, et al. The coiled-coil domain and Tyr177 of bcr are required to induce a murine chronic myelogenous leukemia-like disease by bcr/abl. Blood 2002;99(8):2957-68.
42. McWhirter JR, Galasso DL, Wang JY. A coiled-coil oligomerization domain of Bcr is essential for the transforming function of Bcr-Abl oncoproteins. Mol Cell Biol 1993;13(12):7587-95.
43. Smith KM, Yacobi R, Van Etten RA. Autoinhibition of Bcr-Abl through its SH3 domain. Mol Cell 2003;12(1):27-37.
44. Abelson HT, Rabstein LS. Lymphosarcoma: virus-induced thymic-independent disease in mice. Cancer Res 1970;30(8):2213-22.
45. Feller SM, Knudsen B, Hanafusa H. c-Abl kinase regulates the protein binding activity of c-Crk. EMBO J 1994;13(10):2341-51.
46. Sattler M, Salgia R, Okuda K, Uemura N, Durstin MA, Pisick E, 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(4):839-46.
47. Kipreos ET, Wang JY. Cell cycle-regulated binding of c-Abl tyrosine kinase to DNA. Science 1992;256(5055):382-5.
48. Wen ST, Jackson PK, Van Etten RA. The cytostatic function of c-Abl is controlled by multiple nuclear localization signals and requires the p53 and Rb tumor suppressor gene products. EMBO J 1996;15(7):1583-95.
49. Taagepera S, McDonald D, Loeb JE, Whitaker LL, McElroy AK, Wang JY, et al. Nuclearcytoplasmic shuttling of C-ABL tyrosine kinase. Proc Natl Acad Sci USA 1998;95(13):7457-62.
50. Barila D, Superti-Furga G. An intramolecular SH3-domain interaction regulates c-Abl activity. Nat Genet 1998;18(3):280-2.
51. Pluk H, Dorey K, Superti-Furga G. Autoinhibition of c-Abl. Cell 2002;108(2):247-59.
52. Hantschel O, Nagar B, Guettler S, Kretzschmar J, Dorey K, Kuriyan J, et al. A myristoyl/phosphotyrosine switch regulates c-Abl. Cell 2003;112(6):845-57.
53. Van Etten RA, Jackson P, Baltimore D. The mouse type IV c-abl gene product is a nuclear protein, and activation of transforming ability is associated with cytoplasmic localization. Cell 1989;58(4):669-78.
54. Yuan ZM, Shioya H, Ishiko T, Sun X, Gu J, Huang YY, et al. p73 is regulated by tyrosine kinase c-Abl in the apoptotic response to DNA damage. Nature 1999;399(6738):814-7.
55. Lewis JM, Schwartz MA. Integrins regulate the association and phosphorylation of paxillin by c-Abl. J Biol Chem 1998;273(23):14225-30.
56. Thomas SM, Brugge JS. Cellular functions regulated by Src family kinases. Annu Rev Cell Dev Biol 1997;13:513-609.
57. Franz WM, Berger P, Wang JY. Deletion of an N-terminal regulatory domain of the c-abl tyrosine kinase activates its oncogenic potential. EMBO J 1989;8(1):137-47.
58. Jackson P, Baltimore D. N-terminal mutations activate the leukemogenic potential of the myristoylated form of c-abl. EMBO J 1989;8(2):449-56.
59. Muller AJ, Pendergast AM, Parmar K, Havlik MH, Rosenberg N, Witte ON. En bloc substitution of the Src homology region 2 domain activates the transforming potential of the c-Abl protein tyrosine kinase. Proc Natl Acad Sci USA 1993;90(8):3457-61.
60. Nagar B, Hantschel O, Young MA, Scheffzek K, Veach D, Bornmann W, et al. Structural basis for the autoinhibition of c-Abl tyrosine kinase. Cell 2003;112(6):859-71.
61. Mayer BJ, Baltimore D. Mutagenic analysis of the roles of SH2 and SH3 domains in regulation of the Abl tyrosine kinase. Mol Cell Biol 1994;14(5):2883-94.
62. Pendergast AM, Muller AJ, Havlik MH, Clark R, McCormick F, Witte ON. Evidence for regulation of the human ABL tyrosine kinase by a cellular inhibitor. Proc Natl Acad Sci USA 1991;88(13):5927-31.
63. Shi Y, Alin K, Goff SP. Abl-interactor-1, a novel SH3 protein binding to the carboxy-terminal portion of the Abl protein, suppresses v-abl transforming activity. Genes Dev 1995;9(21):2583-97.
64. Tamura T, Ishihara M, Lamphier MS, Tanaka N, Oishi I, Aizawa S, et al. An IRF-1-dependent pathway of DNA damage-induced apoptosis in mitogen-activated T lymphocytes. Nature 1995;376(6541):596-9.
65. Wen ST, Van Etten RA. The PAG gene product, a stress-induced protein with antioxidant properties, is an Abl SH3-binding protein and a physiological inhibitor of c-Abl tyrosine kinase activity. Genes Dev 1997;11(19):2456-67.
66. Zhao X, Ghaffari S, Lodish H, Malashkevich VN, Kim PS. Structure of the Bcr-Abl oncoprotein oligomerization domain. Nat Struct Biol 2002;9(2):117-20.
67. Schindler T, Bornmann W, Pellicena P, Miller WT, Clarkson B, Kuriyan J. Structural mechanism for STI-571 inhibition of Abelson tyrosine kinase. Science 2000;289(5486):1938-42.
68. Nagar B, Bornmann WG, Pellicena P, Schindler T, Veach DR, Miller WT, et al. Crystal structures of the kinase domain of c-Abl in complex with the small molecule inhibitors PD173955 and imatinib (STI-571). Cancer Res 2002;62(15):4236-43.
69. Azam M, Latek RR, Daley GQ. Mechanisms of autoinhibition and STI-571/imatinib resistance revealed by mutagenesis of BCR-ABL. Cell 2003;112(6):831-43.
70. McWhirter JR, Wang JY. An actin-binding function contributes to transformation by the Bcr-Abl oncoprotein of Philadelphia chromosome-positive human leukemias. EMBO J 1993;12(4):1533-46.
71. Ilaria Jr RL, Van Etten RA. The SH2 domain of P210BCR/ABL is not required for the transformation of hematopoietic factor-dependent cells. Blood 1995;86(10):3897-904.
72. Shepherd P, Suffolk R, Halsey J, Allan N. Analysis of molecular breakpoint and m-RNA transcripts in a prospective randomized trial of interferon in chronic myeloid leukaemia: no correlation with clinical features, cytogenetic response, duration of chronic phase, or survival. Br J Haematol 1995;89(3):546-54.
73. Rozman C, Urbano Ispizua A, Cervantes F, Rozman M, Colomer D, Feliz P, et al. Analysis of the clinical relevance of the breakpoint location within M-BCR and the type of chimeric mRNA in chronic myelogenous leukemia. Leukemia 1995;9(6):1104-7.
74. Hart MJ, Eva A, Evans T, Aaronson SA, Cerione RA. Catalysis of guanine nucleotide exchange on the CDC42Hs protein by the dbl oncogene product. Nature 1991;354(6351):311-4.
75. Verstovsek S, Lin H, Kantarjian H, Saglio G, de Micheli D, Pane F, et al. Neutrophilic-chronic myeloid leukemia: low levels of p230 BCR/ABL mRNA and undetectable BCR/ABL protein may predict an indolent course. Cancer 2002;94(9):2416-25.
76. Ahmed S, Lee J, Wen LP, Zhao Z, Ho J, Best A, et al. Breakpoint cluster region gene productrelated domain of n-chimaerin. Discrimination between Rac-binding and GTPase-activating residues by mutational analysis. J Biol Chem 1994;269(26):17642-8.
77. Briz M, Vilches C, Cabrera R, Fores R, Fernandez MN. Typical chronic myelogenous leukemia with e19a2 junction BCR/ABL transcript [letter]. Blood 1997;90(12):5024-5.
78. Wilson G, Frost L, Goodeve A, Vandenberghe E, Peake I, Reilly J. BCR-ABL transcript with an e19a2 (c3a2) junction in classical chronic myeloid leukemia [letter]. Blood 1997;89(8):3064.
79. Verfaillie CM, Hurley R, Lundell BI, Zhao C, Bhatia R. Integrin-mediated regulation of hematopoiesis: do BCR/ABL-induced defects in integrin function underlie the abnormal circulation and proliferation of CML progenitors? Acta Haematol 1997;97(1-2):40-52.
80. Gordon MY, Dowding CR, Riley GP, Goldman JM, Greaves MF. Altered adhesive interactions with marrow stroma of haematopoietic progenitor cells in chronic myeloid leukaemia. Nature 1987;328(6128):342-4.
81. Verfaillie CM, Hurley R, Zhao RC, Prosper F, Delforge M, Bhatia R. Pathophysiology of CML: do defects in integrin function contribute to the premature circulation and massive expansion of the BCR/ABL positive clone? J Lab Clin Med 1997;129(6):584-91.
82. Durig J, Testa NG, Lord BI, Kasper C, Chang J, Telford N, et al. Characterisation of the differential response of normal and CML haemopoietic progenitor cells to macrophage inflammatory protein-1alpha. Leukemia 1999;13(12):2012-22.
83. Bazzoni G, Carlesso N, Griffin JD, Hemler ME. Bcr/Abl expression stimulates integrin function in hematopoietic cell lines. J Clin Invest 1996;98(2):521-8.
84. Kramer A, Horner S, Willer A, Fruehauf S, Hochhaus A, Hallek M, et al. Adhesion to fibronectin stimulates proliferation of wild-type and bcr/abl-transfected murine hematopoietic cells. Proc Natl Acad Sci USA 1999;96(5):2087-92.
85. Lewis JM, Baskaran R, Taagepera S, Schwartz MA, Wang JY. Integrin regulation of c-Abl tyrosine kinase activity and cytoplasmic-nuclear transport. Proc Natl Acad Sci USA 1996;93(26):15174-9.
86. Uemura N, Salgia R, Ewaniuk DS, Little MT, Griffin JD. Involvement of the adapter protein CRKL in integrin-mediated adhesion. Oncogene 1999;18(22):3343-53.
87. Sattler M, Salgia R, Shrikhande G, Verma S, Uemura N, Law SF, et al. Differential signaling after beta1 integrin ligation is mediated through binding of CRKL to p120(CBL) and p110(HEF1). J Biol Chem 1997;272(22):14320-6.
88. Deininger MW, Vieira S, Mendiola R, Schultheis B, Goldman JM, Melo JV. BCR-ABL tyrosine kinase activity regulates the expression of multiple genes implicated in the pathogenesis of chronic myeloid leukemia. Cancer Res 2000;60(7):2049-55.
89. Wertheim JA, Forsythe K, Druker BJ, Hammer D, Boettiger D, Pear WS. BCR-ABL-induced adhesion defects are tyrosine kinase-independent. Blood 2002;99(11):4122-30.
90. Bhatia R, Wayner EA, McGlave PB, Verfaillie CM. Interferon-alpha restores normal adhesion of chronic myelogenous leukemia hematopoietic progenitors to bone marrow stroma by correcting impaired beta 1 integrin receptor function. J Clin Invest 1994;94(1):384-91.
91. Deininger MW, Goldman JM, Melo JV. The molecular biology of chronic myeloid leukemia. Blood 2000;96(10):3343-56.
92. Puil L, Liu J, Gish G, Mbamalu G, Bowtell D, Pelicci PG, et al. Bcr-Abl oncoproteins bind directly to activators of the Ras signalling pathway. EMBO J 1994;13(4):764-73.
93. Pelicci G, Lanfrancone L, Salcini AE, Romano A, Mele S, Grazia BM, et al. Constitutive phosphorylation of Shc proteins in human tumors. Oncogene 1995;11(5):899-907.
94. Oda T, Heaney C, Hagopian JR, Okuda K, Griffin JD, Druker BJ. Crkl is the major tyrosine-phosphorylated protein in neutrophils from patients with chronic myelogenous leukemia. J Biol Chem 1994;269(37):22925-8.
95. Senechal K, Halpern J, Sawyers CL. The CRKL adaptor protein transforms fibroblasts and functions in transformation by the BCR-ABL oncogene. J Biol Chem 1996;271(38):23255-61.
96. Bhat A, Kolibaba K, Oda T, Ohno Jones S, Heaney C, Druker BJ. Interactions of CBL with BCR-ABL and CRKL in BCR-ABL-transformed myeloid cells. J Biol Chem 1997;272(26):16170-5.
97. Marais R, Light Y, Paterson HF, Marshall CJ. Ras recruits Raf-1 to the plasma membrane for activation by tyrosine phosphorylation. EMBO J 1995;14(13):3136-45.
98. Sattler M, Mohi MG, Pride YB, Quinnan LR, Malouf NA, Podar K, et al. Critical role for Gab2 in transformation by BCR/ABL. Cancer Cell 2002;1(5):479-92.
99. Cortez D, Reuther G, Pendergast AM. The Bcr-Abl tyrosine kinase activates mitogenic signaling pathways and stimulates G1-to-S phase transition in hematopoietic cells. Oncogene 1997;15(19):2333-42.
100. 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(24):5887-95.
101. Raitano AB, Halpern JR, Hambuch TM, Sawyers CL. The Bcr-Abl leukemia oncogene activates Jun kinase and requires Jun for transformation. Proc Natl Acad Sci USA 1995;92(25):11746-50.
102. Cahill MA, Janknecht R, Nordheim A. Signalling pathways: jack of all cascades. Curr Biol 1996;6(1):16-9.
103. Mayer IA, Verma A, Grumbach IM, Uddin S, Lekmine F, Ravandi F, et al. The p38 MAPK pathway mediates the growth inhibitory effects of interferon-alpha in BCR-ABL-expressing cells. J Biol Chem 2001;276(30):28570-7.
104. Ilaria Jr 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(49):31704-10.
105. Chai SK, Nichols GL, Rothman P. Constitutive activation of JAKs and STATs in BCR-Ablexpressing cell lines and peripheral blood cells derived from leukemic patients. J Immunol 1997;159(10):4720-8.
106. Horvath CM. STAT proteins and transcriptional responses to extracellular signals. Trends Biochem Sci 2000;25(10):496-502.
107. Klejman A, Rushen L, Morrione A, Slupianek A, Skorski T. Phosphatidylinositol-3 kinase inhibitors enhance the anti-leukemia effect of STI571. Oncogene 2002;21(38):5868-76.
108. de Groot RP, Raaijmakers JA, Lammers JW, Jove R, Koenderman L. STAT5 activation by BCR-Abl contributes to transformation of K562 leukemia cells. Blood 1999;94(3):1108-12.
109. Horita M, Andreu EJ, Benito A, Arbona C, Sanz C, Benet I, 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-x(L) [in process citation]. J Exp Med 2000;191(6):977-84.
110. Sillaber C, Gesbert F, Frank DA, Sattler M, Griffin JD. STAT5 activation contributes to growth and viability in Bcr/Abl- transformed cells. Blood 2000;95(6):2118-25.
111. Gesbert F, Sellers WR, Signoretti S, Loda M, Griffin JD. BCR/ABL regulates expression of the cyclin-dependent kinase inhibitor p27Kip1 through the phosphatidylinositol 3-kinase/AKT pathway. J Biol Chem 2000;275(50):39223- 30.
112. Sexl V, Piekorz R, Moriggl R, Rohrer J, Brown MP, Bunting KD, et al. Stat5a/b contribute to interleukin 7-induced B-cell precursor expansion, but abl- and bcr/abl-induced transformation are independent of stat5. Blood 2000;96(6):2277-83.
113. Skorski T, Kanakaraj P, Nieborowska-Skorska M, Ratajczak MZ, Wen SC, Zon G, et al. Phosphatidylinositol-3 kinase activity is regulated by BCR/ABL and is required for the growth of Philadelphia chromosome-positive cells. Blood 1995;86(2):726-36.
114. Skorski T, Bellacosa A, Nieborowska-Skorska M, Majewski M, Martinez R, Choi JK, et al. Transformation of hematopoietic cells by BCR/ABL requires activation of a PI-3k/Akt-dependent pathway. EMBO J 1997;16(20):6151-61.
115. Komatsu N, Watanabe T, Uchida M, Mori M, Kirito K, Kikuchi S, et al. A member of Forkhead transcription factor FKHRL1 is a downstream effector of STI571-induced cell cycle arrest in BCR-ABL-expressing cells. J Biol Chem 2003;278(8):6411-9.
116. Jonuleit T, van der Kuip H, Miething C, Michels H, Hallek M, Duyster J, et al. Bcr-Abl kinase down-regulates cyclin-dependent kinase inhibitor p27 in human and murine cell lines. Blood 2000;96(5):1933-9.
117. Franke TF, Kaplan DR, Cantley LC. PI3K: downstream AKTion blocks apoptosis. Cell 1997;88(4):435-7.
118. del Peso L, Gonzalez-Garcia M, Page C, Herrera R, Nunez G. Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. Science 1997;278(5338):687-9.
119. Neshat MS, Raitano AB, Wang HG, Reed JC, Sawyers CL. The survival function of the Bcr-Abl oncogene is mediated by Bad-dependent and-independent pathways: roles for phosphatidylinositol 3- kinase and Raf. Mol Cell Biol 2000;20(4):1179-86.
120. Menssen A, Hermeking H. Characterization of the c-MYC-regulated transcriptome by SAGE: identification and analysis of c-MYC target genes. Proc Natl Acad Sci USA 2002;99(9):6274-9.
121. Sawyers CL, Callahan W, Witte ON. Dominant negative MYC blocks transformation by ABL oncogenes. Cell 1992;70(6):901-10.
122. Afar DE, Goga A, McLaughlin J, Witte ON, Sawyers CL. Differential complementation of Bcr-Abl point mutants with c-Myc. Science 1994;264(5157):424-6.
123. Okuda K, D'Andrea A, Van Etten RA, Griffin JD. The C-terminus of c-ABL is required for proliferation and viability signaling in a c-ABL/erythropoietin receptor fusion protein. Blood 1998;92(10):3848-56.
124. Xie S, Wang Y, Liu J, Sun T, Wilson MB, Smithgall TE, et al. Involvement of Jak2 tyrosine phosphorylation in Bcr-Abl transformation. Oncogene 2001;20(43):6188-95.
125. Daley GQ, Baltimore D. Transformation of an interleukin 3-dependent hematopoietic cell line by the chronic myelogenous leukemia-specific P210bcr/abl protein. Proc Natl Acad Sci USA 1988;85(23):9312-6.
126. Sirard C, Laneuville P, Dick JE. Expression of bcr-abl abrogates factor-dependent growth of human hematopoietic M07E cells by an autocrine mechanism. Blood 1994;83(6):1575-85.
127. Bedi A, Zehnbauer BA, Barber JP, Sharkis SJ, Jones RJ. Inhibition of apoptosis by BCR-ABL in chronic myeloid leukemia. Blood 1994;83(8):2038-44.
128. Bedi A, Barber JP, Bedi GC, el Deiry WS, Sidransky D, Vala MS, et al. BCR-ABL-mediated inhibition of apoptosis with delay of G2/M transition after DNA damage: a mechanism of resistance to multiple anticancer agents. Blood 1995;86(3):1148-58.
129. Amos TA, Lewis JL, Grand FH, Gooding RP, Goldman JM, Gordon MY. Apoptosis in chronic myeloid leukaemia: normal responses by progenitor cells to growth factor deprivation, X-irradiation and glucocorticoids. Br J Haematol 1995;91(2):387-93.
130. Amarante-Mendes GP, Naekyung KC, Liu L, Huang Y, Perkins CL, Green DR, et al. Bcr-Abl exerts its antiapoptotic effect against diverse apoptotic stimuli through blockage of mitochondrial release of cytochrome C and activation of caspase-3. Blood 1998;91(5):1700-5.
131. Dubrez L, Eymin B, Sordet O, Droin N, Turhan AG, Solary E. BCR-ABL delays apoptosis upstream of procaspase-3 activation. Blood 1998;91(7):2415-22.
132. Sanchez-Garcia I, Martin-Zanca D. Regulation of Bcl-2 gene expression by BCR-ABL is mediated by Ras. J Mol Biol 1997;267(2):225-8.
133. Wang HG, Rapp UR, Reed JC. Bcl-2 targets the protein kinase Raf-1 to mitochondria. Cell 1996;87(4):629-38.
134. Zha J, Harada H, Yang E, Jockel J, Korsmeyer SJ. Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L) [comments]. Cell 1996;87(4):619-28.
135. Gabriele L, Phung J, Fukumoto J, Segal D, Wang IM, Giannakakou P, et al. Regulation of apoptosis in myeloid cells by interferon consensus sequence-binding protein. J Exp Med 1999;190(3):411-21.
136. Hao SX, Ren R. Expression of interferon consensus sequence binding protein (ICSBP) is downregulated in Bcr-Abl-induced murine chronic myelogenous leukemia-like disease, and forced coexpression of ICSBP inhibits Bcr-Abl-induced myeloproliferative disorder. Mol Cell Biol 2000;20(4):1149-61.
137. Burchert A, Cai D, Hofbauer L, Samuelsson MK, Slater EP, Duyster J, et al. Interferon consensus sequence binding protein (ICSBP, IRF-8) antagonizes BCR/ABL and down-regulates bcl-2. Blood 2003;103:3480-9.
138. Vigneri P, Wang JY. Induction of apoptosis in chronic myelogenous leukemia cells through nuclear entrapment of BCR-ABL tyrosine kinase. Nat Med 2001;7(2):228-34.
139. Melo JV. Inviting leukemic cells to waltz with the devil. Nat Med 2001;7(2):156-7.
140. Bueno-da-Silva AE, Brumatti G, Russo FO, Green DR, Amarante-Mendes GP. Bcr-Abl-mediated resistance to apoptosis is independent of constant tyrosine-kinase activity. Cell Death Differ 2003;10(5):592-8.
141. Lange T, Niederwieser DW, Deininger MW. Residual disease in chronic myeloid leukemia after induction of molecular remission. N Engl J Med 2003;349(15):1483-4.
142. Dai Z, Quackenbush RC, Courtney KD, Grove M, Cortez D, Reuther GW, et al. Oncogenic Abl and Src tyrosine kinases elicit the ubiquitin-dependent degradation of target proteins through a Ras-independent pathway. Genes Dev 1998;12(10):1415-24.
143. Deutsch E, Dugray A, AbdulKarim B, Marangoni E, Maggiorella L, Vaganay S, et al. BCRABL down-regulates the DNA repair protein DNA-PKcs. Blood 2001;97(7):2084-90.
144. Oetzel C, Jonuleit T, Gotz A, van der Kuip H, Michels H, Duyster J, et al. The tyrosine kinase inhibitor CGP 57148 (ST1 571) induces apoptosis in BCR-ABL-positive cells by down-regulating BCL-X. Clin Cancer Res 2000;6(5):1958-68.
145. Goetz AW, van der Kuip H, Maya R, Oren M, Aulitzky WE. Requirement for Mdm2 in the survival effects of Bcr-Abl and interleukin 3 in hematopoietic cells. Cancer Res 2001;61(20):7635-41.
146. Wilda M, Fuchs U, Wossmann W, Borkhardt A. Killing of leukemic cells with a BCR/ABL fusion gene by RNA interference (RNAi). Oncogene 2002;21(37):5716-24.
147. Scherr M, Battmer K, Winkler T, Heidenreich O, Ganser A, Eder M. Specific inhibition of bcr-abl gene expression by small interfering RNA. Blood 2003;101(4):1566-9.
148. Wohlbold L, van der Kuip H, Miething C, Vornlocher HP, Knabbe C, Duyster J, et al. Inhibition of bcr-abl gene expression by small interfering RNA sensitizes for imatinib mesylate (STI571). Blood 2003;102(6):2236-9.
149. Nimmanapalli R, Bali P, O'Bryan E, Fuino L, Guo F, Wu J, et al. Arsenic trioxide inhibits translation of mRNA of bcr-abl, resulting in attenuation of Bcr-Abl levels and apoptosis of human leukemia cells. Cancer Res 2003;63(22):7950-8.
150. Nimmanapalli R, O'Bryan E, Bhalla K. Geldanamycin and its analogue 17-allylamino-17-demethoxygeldanamycin lowers Bcr-Abl levels and induces apoptosis and differentiation of Bcr-Abl-positive human leukemic blasts. Cancer Res 2001;61(5):1799-804.
151. Nimmanapalli R, Fuino L, Stobaugh C, Richon V, Bhalla K. Cotreatment with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) enhances imatinib-induced apoptosis of Bcr-Abl-positive human acute leukemia cells. Blood 2003;101(8):3236-9.
152. Nimmanapalli R, Fuino L, Bali P, Gasparetto M, Glozak M, Tao J, et al. Histone deacetylase inhibitor LAQ824 both lowers expression and promotes proteasomal degradation of Bcr-Abl and induces apoptosis of imatinib mesylate-sensitive or-refractory chronic myelogenous leukemia-blast crisis cells. Cancer Res 2003;63(16):5126-35.
153. Mow BM, Chandra J, Svingen PA, Hallgren CG, Weisberg E, Kottke TJ, et al. Effects of the Bcr/abl kinase inhibitors STI571 and adaphostin (NSC 680410) on chronic myelogenous leukemia cells in vitro. Blood 2002;99(2):664-71.
154. Dorsey JF, Jove R, Kraker AJ, Wu J. The pyrido[2,3-d]pyrimidine derivative PD180970 inhibits p210Bcr-Abl tyrosine kinase and induces apoptosis of K562 leukemic cells. Cancer Res 2000;60(12):3127-31.
155. La Rosee P, Corbin AS, Stoffregen EP, Deininger MW, Druker BJ. 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(24):7149-53.
156. von Bubnoff N, Veach DR, Miller WT, Li W, Sanger J, Peschel C, et al. Inhibition of wild-type and mutant Bcr-Abl by pyrido-pyrimidine-type small molecule kinase inhibitors. Cancer Res 2003;63(19):6395-404.
157. Hoover RR, Mahon FX, Melo JV, Daley GQ. Overcoming STI571 resistance with the farnesyl transferase inhibitor SCH66336. Blood 2002;100(3):1068-71.
158. Kuroda J, Kimura S, Segawa H, Kobayashi Y, Yoshikawa T, Urasaki Y, et al. The thirdgeneration bisphosphonate zoledronate synergistically augments the anti-Ph+ leukemia activity of imatinib mesylate. Blood 2003;102(6):2229-35.
159. Yu C, Krystal G, Varticovksi L, McKinstry R, Rahmani M, Dent P, et al. Pharmacologic mitogen-activated protein/extracellular signal-regulated kinase kinase/mitogen-activated protein kinase inhibitors interact synergistically with STI571 to induce apoptosis in Bcr/Ablexpressing human leukemia cells. Cancer Res 2002;62(1):188-99.
160. Ly C, Arechiga AF, Melo JV, Walsh CM, Ong ST. Bcr-Abl kinase modulates the translation regulators ribosomal protein S6 and 4E-BP1 in chronic myelogenous leukemia cells via the mammalian target of rapamycin. Cancer Res 2003;63(18):5716-22.
161. Sun X, Layton JE, Elefanty A, Lieschke GJ. Comparison of effects of the tyrosine kinase inhibitors AG957, AG490, and STI571 on BCR-ABL-expressing cells, demonstrating synergy between AG490 and STI571. Blood 2001;97(7):2008-15.
162. Tipping AJ, Melo JV. Imatinib mesylate in combination with other