Receptor tyrosine kinase alterations in AML - Biology and therapy

Cancer Treatment and Research

Volumn 145, Issue , 2010, Pages 85-108

  Stirewalt, Derek L ^a   Meshinchi, Soheil ^b  

^a Fred Hutchinson Cancer Research Center   (United States)

^b NONE

Author keywords

[No Author keywords available]

Indexed keywords

2,4 DIMETHYL 5 (2 OXO 1H INDOL 3 YLMETHYLENE) 3 PYRROLEPROPIONIC ACID; 5,6,7,13 TETRAHYDRO 12 (3 HYDROXYPROPYL) 9 ISOPROPOXYMETHYLINDENO[2,1 A]PYRROLO[3,4 C]CARBAZOL 5(12H) ONE; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; CYTARABINE; DASATINIB; DAUNORUBICIN; GROWTH FACTOR RECEPTOR BOUND PROTEIN 2; IMATINIB; LESTAURTINIB; MAMMALIAN TARGET OF RAPAMYCIN; MIDOSTAURIN; MITOGEN ACTIVATED PROTEIN KINASE; NILOTINIB; PHOSPHATIDYLINOSITOL 3 KINASE; PLATELET DERIVED GROWTH FACTOR ALPHA RECEPTOR; PLATELET DERIVED GROWTH FACTOR RECEPTOR; PROTEIN KINASE B; PROTEIN SH2; PROTEIN TYROSINE KINASE; S6 KINASE; SEMAXANIB; STAT PROTEIN; SU 5614; SUNITINIB; TANDUTINIB; UNCLASSIFIED DRUG; VASCULOTROPIN RECEPTOR 1; VASCULOTROPIN RECEPTOR 2; ANTINEOPLASTIC AGENT; CD135 ANTIGEN; FLT3 PROTEIN, HUMAN; ONCOPROTEIN; PROTEIN KINASE INHIBITOR; STEM CELL FACTOR RECEPTOR; TUMOR PROTEIN;

ACUTE GRANULOCYTIC LEUKEMIA; APOPTOSIS; CELL DIFFERENTIATION; CELL PROLIFERATION; CLINICAL TRIAL; DIMERIZATION; DOWNSTREAM PROCESSING; DRUG INDUCED HEADACHE; DYSPNEA; ENZYME ACTIVATION; FATIGUE; GENE MUTATION; HUMAN; INJECTION SITE REACTION; LIGAND BINDING; MOLECULAR DOCKING; MYELODYSPLASTIC SYNDROME; NAUSEA; NEUTROPENIA; NONHUMAN; POINT MUTATION; PRIORITY JOURNAL; PROGNOSIS; PROTEIN CONFORMATION; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN STRUCTURE; REMISSION; REVIEW; THROMBOSIS; ADULT; ANTAGONISTS AND INHIBITORS; BIOLOGICAL MODEL; DRUG DELIVERY SYSTEM; DRUG EFFECTS; ENZYMOLOGY; FORECASTING; GENE DUPLICATION; GENETICS; LEUKEMIA, MYELOID, ACUTE; MUTATION; PHYSIOLOGY; SIGNAL TRANSDUCTION;

ADULT; ANTINEOPLASTIC AGENTS; DRUG DELIVERY SYSTEMS; FMS-LIKE TYROSINE KINASE 3; FORECASTING; GENE DUPLICATION; HUMANS; LEUKEMIA, MYELOID, ACUTE; MODELS, BIOLOGICAL; MUTATION; NEOPLASM PROTEINS; ONCOGENE PROTEINS, FUSION; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-KIT; RECEPTOR PROTEIN-TYROSINE KINASES; SIGNAL TRANSDUCTION;

EID: 77956154092     PISSN: 09273042     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-0-387-69259-3_6     Document Type: Review

References (182)

1. Abu-Duhier FM, Goodeve AC, Wilson GA, Care RS, Peake IR, Reilly JT. Identification of novel FLT-3 Asp835 mutations in adult acute myeloid leukaemia. Br J Haematol. 2001;113:983-988.
2. Abu-Duhier FM, Goodeve AC, Wilson GA, et al. FLT3 internal tandem duplication mutations in adult acute myeloid leukaemia define a high-risk group. Br J Haematol. 2000;111:190-195.
3. Agnes F, Shamoon B, Dina C, Rosnet O, Birnbaum D, Galibert F. Genomic structure of the downstream part of the human FLT3 gene: exon/intron structure conservation among genes encoding receptor tyrosine kinases (RTK) of subclass III. Gene. 1994;145:283-288.
4. Aguayo A, Estey E, Kantarjian H, et al. Cellular vascular endothelial growth factor is a predictor of outcome in patients with acute myeloid leukemia. Blood. 1999;94: 3717-3721.
5. Anstrom KJ, Reed SD, Allen AS, Glendenning GA, Schulman KA. Long-term survival estimates for imatinib versus interferon-alpha plus low-dose cytarabine for patients with newly diagnosed chronic-phase chronic myeloid leukemia. Cancer. 2004;101:2584-2592.
6. Armstrong SA, Kung AL, Mabon ME, et al. Inhibition of FLT3 in MLL. Validation of a therapeutic target identified by gene expression based classification. Cancer Cell. 2003;3:173-183.
7. Armstrong SA, Staunton JE, Silverman LB, et al. MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia. Nat Genet. 2002;30:41-47.
8. Beghini A, Larizza L, Cairoli R, Morra E. c-kit activating mutations and mast cell proliferation in human leukemia. Blood. 1998;92:701-702.
9. Beghini A, Peterlongo P, Ripamonti CB, et al. C-kit mutations in core binding factor leukemias. Blood. 2000;95:726-727.
10. Beghini A, Ripamonti CB, Cairoli R, et al. KIT activating mutations: incidence in adult and pediatric acute myeloid leukemia, and identification of an internal tandem duplication. Haematologica. 2004;89:920-925.
11. Beghini A, Ripamonti CB, Castorina P, et al. Trisomy 4 leading to duplication of a mutated KIT allele in acute myeloid leukemia with mast cell involvement. Cancer Genet Cytogenet. 2000;119:26-31.
12. Bentires-Alj M, Paez JG, David FS, et al. Activating mutations of the noonan syndromeassociated SHP2/PTPN11 gene in human solid tumors and adult acute myelogenous leukemia. Cancer Res. 2004;64:8816-8820.
13. Birkenkamp KU, Geugien M, Lemmink HH, Kruijer W, Vellenga E. Regulation of constitutive STAT5 phosphorylation in acute myeloid leukemia blasts. Leukemia. 2001; 15:1923-1931.
14. Blume-Jensen P, Hunter T. Oncogenic kinase signalling. Nature. 2001;411:355-365.
15. Bos JL. Ras oncogenes in human cancer: a review. Cancer Res. 1989;49:4682-4689.
16. Boultwood J, Rack K, Kelly S, et al. Loss of both CSF1R (FMS) alleles in patients with myelodysplasia and a chromosome 5 deletion. Proc Natl Acad Sci USA. 1991;88:6176-6180.
17. Bowen DT, Frew ME, Hills R, et al. RAS mutation in acute myeloid leukemia is associated with distinct cytogenetic subgroups but does not influence outcome in patients younger than 60 years. Blood. 2005;106:2113-2119.
18. Brandts CH, Sargin B, Rode M, et al. Constitutive activation of Akt by Flt3 internal tandem duplications is necessary for increased survival, proliferation, and myeloid transformation. Cancer Res. 2005;65:9643-9650.
19. Cairoli R, Beghini A, Grillo G, et al. Prognostic impact of c-KIT mutations in core binding factor leukemias. An Italian retrospective study. Blood. 2006. In press.
20. Cairoli R, Beghini A, Morello E, et al. Imatinib mesylate in the treatment of Core Binding Factor leukemias withKIT mutations. A report of three cases. Leuk Res. 2005;29:397-400.
21. Cairoli R, Grillo G, Beghini A, et al. C-Kit point mutations in core binding factor leukemias: correlation with white blood cell count and the white blood cell index. Leukemia. 2003;17:471-472.
22. Callens C, Chevret S, Cayuela JM, et al. Prognostic implication of FLT3 and Ras gene mutations in patients with acute promyelocytic leukemia (APL): a retrospective study from the European APL Group. Leukemia. 2005;19:1153-1160.
23. Cammenga J, Horn S, Bergholz U, et al. Extracellular KIT receptor mutants, commonly found in core binding factor AML, are constitutively active and respond to imatinib mesylate. Blood. 2005;106:3958-3961.
24. Care RS, Valk PJ, Goodeve AC, et al. Incidence and prognosis of c-KIT and FLT3 mutations in core binding factor (CBF) acute myeloid leukaemias. Br J Haematol. 2003; 121:775-777.
25. Carroll M, Tomasson MH, Barker GF, Golub TR, Gilliland DG. The TEL/plateletderived growth factor beta receptor (PDGF beta R) fusion in chronic myelomonocytic leukemia is a transforming protein that self-associates and activates PDGF beta R kinase-dependent signaling pathways. Proc Natl Acad Sci USA. 1996;93:14845-14850.
26. Casey G, Rudzki Z, Roberts M, Hutchins C, Juttner C. N-ras mutation in acute myeloid leukemia: incidence, prognostic significance and value as a marker of minimal residual disease. Pathology. 1993;25:57-62.
27. Christiansen DH, Andersen MK, Desta F, Pedersen-Bjergaard J. Mutations of genes in the receptor tyrosine kinase (RTK)/RAS-BRAF signal transduction pathway in therapyrelated myelodysplasia and acute myeloid leukemia. Leukemia. 2005;19:2232-2240.
28. Cools J, DeAngelo DJ, Gotlib J, et al. A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med. 2003;348:1201-1214.
29. Cools J, Stover EH, Gilliland DG. Detection of the FIP1L1-PDGFRA fusion in idiopathic hypereosinophilic syndrome and chronic eosinophilic leukemia. Methods Mol Med. 2006;125:177-187.
30. Cools J, Stover EH, Wlodarska I, Marynen P, Gilliland DG. The FIP1L1-PDGFRalpha kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia. Curr Opin Hematol. 2004;11:51-57.
31. De Angelo DJ, Stone RM, Heaney ML, et al. Phase II evaluation of the tyrosine kinase inhibitor MLN518 in patients with acute myeloid leukemia (AML) bearing a FLT3 internal tandem duplication (ITD) mutation. Blood. 2004;104:1792a.
32. Dello Sbarba P, Pollard JW, Stanley ER. Alterations in CSF-1 receptor expression and protein tyrosine phosphorylation in autonomous mutants of a CSF-1 dependent macrophage cell line. Growth Factors. 1991;5:75-85.
33. Druker BJ, Lydon NB. Lessons learned from the development of an abl tyrosine kinase inhibitor for chronic myelogenous leukemia. J Clin Invest. 2000;105:3-7.
34. Druker BJ, Sawyers CL, Kantarjian H, et al. Activity of a specific inhibitor of the BCRABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med. 2001;344:1038-1042.
35. Farr CJ, Saiki RK, Erlich HA, McCormick F, Marshall CJ. Analysis of RAS gene mutations in acute myeloid leukemia by polymerase chain reaction and oligonucleotide probes. Proc Natl Acad Sci USA. 1988;85:1629-1633.
36. Felgner J, Kreipe H, Heidorn K, et al. Increased methylation of the c-fms protooncogene in acute myelomonocytic leukemias. Pathobiology. 1991;59:293-298.
37. Fenski R, Flesch K, Serve S, et al. Constitutive activation of FLT3 in acute myeloid leukaemia and its consequences for growth of 32D cells. Br JHaematol. 2000;108:322-330.
38. Foran J, OFarrell AM, Fiedler W, et al. An innovative single dose clinical study shows potent inhibition of FLT3 phosphorylation by SU11248 in vivo: a clinical and pharmacodynamic study in AML patients. Blood. 2002;100:2196a.
39. Foran J, Paquette R, Cooper M, et al. A phase I study of repeated oral dosing with SU11248 for the treatment of patients with acute myeloid leukemia who have failed, or are not eligible for conventional chemotherapy. Blood. 2002;100:2195a.
40. Forrester K, Almoguera C, Han K, Grizzle WE, Perucho M. Detection of high incidence of K-ras oncogenes during human colon tumorigenesis. Nature. 1987;327:298-303.
41. Frohling S, Schlenk RF, Breitruck J, et al. Prognostic significance of activating FLT3 mutations in younger adults (16 to 60 years) with acute myeloid leukemia and normal cytogenetics: a study of the AML Study Group Ulm. Blood. 2002;100:4372-4380.
42. Furitsu T, Tsujimura T, Tono T, et al. Identification of mutations in the coding sequence of the proto-oncogene c-kit in a human mast cell leukemia cell line causing ligand-independent activation of c-kit product. J Clin Invest. 1993;92:1736-1744.
43. Furuta T, Sakai T, Senga T, et al. Identification of potent and selective inhibitors of PDGF receptor autophosphorylation. J Med Chem. 2006;49:2186-2192.
44. Gabbianelli M, Pelosi E, Montesoro E, et al. Multi-level effects of flt3 ligand on human hematopoiesis: expansion of putative stem cells and proliferation of granulomonocytic progenitors/monocytic precursors. Blood. 1995;86:1661-1670.
45. Gari M, Goodeve A, Wilson G, et al. c-kit proto-oncogene exon 8 in-frame deletion plus insertion mutations in acute myeloid leukaemia. Br J Haematol. 1999;105:894-900.
46. Giles F, Schiffer C, Kantarjian H, et al. Phase 1 study of PKC412, an oral FLT3 kinase inhibitor, in sequential and concomitant combinations with daunorubicin and cytarabine (DA) induction and high-dose cytarabine consolidation in newly diagnosed patients with AML. Blood. 2004;104:262a.
47. Giles FJ, Stopeck AT, Silverman LR, et al. SU5416, a small molecule tyrosine kinase receptor inhibitor, has biologic activity in patients with refractory acute myeloid leukemia or myelodysplastic syndromes. Blood. 2003;102:795-801.
48. Gille H, Kowalski J, Yu L, et al. A repressor sequence in the juxtamembrane domain of Flt-1 (VEGFR-1) constitutively inhibits vascular endothelial growth factor-dependent phosphatidylinositol 30-kinase activation and endothelial cell migration. Embo J. 2000; 19:4064-4073.
49. Goemans BF, Zwaan CM, Miller M, et al.Mutations in KIT and RAS are frequent events in pediatric core-binding factor acute myeloid leukemia. Leukemia. 2005;19: 1536-1542.
50. Golub TR, Barker GF, Lovett M, Gilliland DG. Fusion of PDGF receptor beta to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation. Cell. 1994;77:307-316.
51. Gotlib J, Cools J, Malone JM, 3rd, Schrier SL, Gilliland DG, Coutre SE. The FIP1L1-PDGFRalpha fusion tyrosine kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia: implications for diagnosis, classification, and management. Blood. 2004;103:2879-2891.
52. Griffith J, Black J, Faerman C, et al. The structural basis for autoinhibition of FLT3 by the juxtamembrane domain. Mol Cell. 2004;13:169-178.
53. Grundler R, Miething C, Thiede C, Peschel C, Duyster J. FLT3-ITD and tyrosine kinase domain mutants induce 2 distinct phenotypes in a murine bone marrow transplantation model. Blood. 2005;105:4792-4799.
54. Hayakawa F, Towatari M, Kiyoi H, et al. Tandem-duplicated Flt3 constitutively activates STAT5 andMAPkinase and introduces autonomous cell growth in IL-3-dependent cell lines. Oncogene. 2000;19:624-631.
55. Heinrich MC, Druker BJ, Curtin PT, et al.A"first in man" study of the safety and PK/PD of an oral FLT3 inhibitor (MLN518) in patients with AML or high risk myelodyspsia. Blood. 2002;100:1305a.
56. Heinrich MC, Griffith DJ, Druker BJ, Wait CL, Ott KA, Zigler AJ. Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor. Blood. 2000;96:925-932.
57. Hochhaus A, Kreil S, Corbin AS, et al. Molecular and chromosomal mechanisms of resistance to imatinib (STI571) therapy. Leukemia. 2002;16:2190-2196.
58. 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;349:1423-1432.
59. Iwai T, Yokota S, Nakao M, et al. Internal tandem duplication of the FLT3 gene and clinical evaluation in childhood acute myeloid leukemia. The Childrens Cancer and Leukemia Study Group, Japan. Leukemia. 1999;13:38-43.
60. Janssen JW, Steenvoorden AC, Lyons J, et al. RAS gene mutations in acute and chronic myelocytic leukemias, chronic myeloproliferative disorders, and myelodysplastic syndromes. Proc Natl Acad Sci USA. 1987;84:9228-9232.
61. Karp JE, Lancet JE, Kaufmann SH, et al. Clinical and biologic activity of the farnesyltransferase inhibitor R115777 in adults with refractory and relapsed acute leukemias: a phase 1 clinical-laboratory correlative trial. Blood. 2001;97:3361-3369.
62. Karp JE, Lancet JE. Development of the farnesyltransferase inhibitor tipifarnib for therapy of hematologic malignancies. Fut Oncol. 2005;1:719-731.
63. Karp JE, Lancet JE. Targeting the process of farnesylation for therapy of hematologic malignancies. Curr Mol Med. 2005;5:643-652.
64. Kelly LM, Kutok JL, Williams IR, et al. PML/RARalpha and FLT3-ITD induce an APL-like disease in a mouse model. Proc Natl Acad Sci USA. 2002;99:8283-8288.
65. Kelly LM, Liu Q, Kutok JL, Williams IR, Boulton CL, Gilliland DG. FLT3 internal tandem duplication mutations associated with human acute myeloid leukemias induce myeloproliferative disease in a murine bone marrow transplant model. Blood. 2002;99: 310-318.
66. Kelly LM, Yu J, Boulton CL, et al. CT53518, a novel selective FLT3 antagonist for the treatment of acute myelogenous leukemia (AML). Caner Cell. 2002.
67. Kindler T, Breitenbuecher F, Kasper S, et al. Identification of a novel activating mutation (Y842C) within the activation loop of FLT3 in patients with acute myeloid leukemia (AML). Blood. 2005;105:335-340.
68. Kitayama H, Kanakura Y, Furitsu T, et al. Constitutively activating mutations of c-kit receptor tyrosine kinase confer factor-independent growth and tumorigenicity of factordependent hematopoietic cell lines. Blood. 1995;85:790-798.
69. Kiyoi H, Naoe T, Nakano Y, et al. Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia. Blood. 1999;93:3074-3080.
70. Kiyoi H, Ohno R, Ueda R, Saito H, Naoe T. Mechanism of constitutive activation of FLT3 with internal tandem duplication in the juxtamembrane domain. Oncogene. 2002;21:2555-2563.
71. Kiyoi H, Towatari M, Yokota S, et al. Internal tandem duplication of the FLT3 gene is a novel modality of elongation mutation which causes constitutive activation of the product. Leukemia. 1998;12:1333-1337.
72. Kohl TM, Schnittger S, Ellwart JW,Hiddemann W, Spiekermann K.KIT exon 8 mutations associated with core-binding factor (CBF)-acute myeloid leukemia (AML) cause hyperactivation of the receptor in response to stem cell factor. Blood. 2005;105:3319-3321.
73. Kondo M, Horibe K, Takahashi Y, et al. Prognostic value of internal tandem duplication of the FLT3 gene in childhood acute myelogenous leukemia. Med Pediatr Oncol. 1999;33:525-529.
74. Kottaridis PD, Gale RE, Frew ME, et al. The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood. 2001;98:1752-1759.
75. Kottaridis PD, Gale RE, Langabeer SE, Frew ME, Bowen DT, Linch DC. Studies of FLT3 mutations in paired presentation and relapse samples from patients with acute myeloid leukemia: implications for the role of FLT3 mutations in leukemogenesis, minimal residual disease detection, and possible therapy with FLT3 inhibitors. Blood. 2002;100:2393-2398
76. Kubo K, Naoe T, Kiyoi H, et al. Clonal analysis of multiple point mutations in the N-ras gene in patients with acute myeloid leukemia. Jpn J Cancer Res. 1993;84:379-387.
77. Kuchenbauer F, Feuring-Buske M, Buske C. AML1-ETO needs a partner: new insights into the pathogenesis of t(8;21) leukemia. Cell Cycle. 2005;4:1716-1718.
78. Lacayo NJ, Meshinchi S, Kinnunen P, et al. Gene Expression Profiles at Diagnosis in de novo Childhood AML Patients Identify FLT3 Mutations with Good Clinical Outcomes. Blood. 2004.
79. Lancet JE, Karp JE. Farnesyltransferase inhibitors in hematologic malignancies: new horizons in therapy. Blood. 2003;102:3880-3889.
80. Levis M, Allebach J, Fai-Tse K, et al. FLT3-targeted inhibitors kill FLT3-dependent modeled cells, leukemia-derived cell lines, and primary AML blasts in vitro and in vivo. Blood. 2001;89:721a.
81. Levis M, Allebach J, Tse KF, et al. A FLT3-targeted tyrosine kinase inhibitor is cytotoxic to leukemia cells in vitro and in vivo. Blood. 2002;99:3885-3891.
82. Levis M, Pham R, Smith BD, Small D. In vitro studies of a FLT3 inhibitor combined with chemotherapy: sequence of administration is important in order to achieve synergistic cytotoxic effects. Blood. 2004;104:1145-1150.
83. Levis M, Tse KF, Smith BD, Garrett E, Small D. A FLT3 tyrosine kinase inhibitor is selectively cytotoxic to acute myeloid leukemia blasts harboring FLT3 internal tandem duplication mutations. Blood. 2001;98:885-887.
84. Liang DC, Shih LY, Fu JF, et al. K-Ras mutations and N-Ras mutations in childhood acute leukemias with or without mixed-lineage leukemia gene rearrangements. Cancer. 2006;106:950-956.
85. Longley BJ, Jr., Metcalfe DD, Tharp M, et al. Activating and dominant inactivating c-KIT catalytic domain mutations in distinct clinical forms of human mastocytosis. Proc Natl Acad Sci USA. 1999;96:1609-1614.
86. McCoy MS, Toole JJ, Cunningham JM, Chang EH, Lowy DR, Weinberg RA. Characterization of a human colon/lung carcinoma oncogene. Nature. 1983;302:79-81.
87. Mead A, Linch D, Hills R, Wheatley K, Burnett A, Gale R. Favourable prognosis associated with FLT3 tyrosine kinase domain mutations in AML in contrast to the adverse outcome associated with internal tandem duplications. Blood. 2005;106:334a.
88. Meshinchi S, Alonzo TA, Gerbing R, Lang B, Radich J. FLT3 internal tandem duplication (FLT3/ITD) is a prognostic factor for poor outcome in pediatric AML: a CCG2961 study. Blood. 2003;102:335a.
89. Meshinchi S, Stirewalt DL, Alonzo TA, et al. Activating mutations of RTK/ras signal transduction pathway in pediatric acute myeloid leukemia. Blood. 2003;102: 1474-1479.
90. Meshinchi S, Woods WG, Stirewalt DL, et al. Prevalence and prognostic significance of FLT3 internal tandem duplication in pediatric acute myeloid leukemia. Blood. 2001;97:89-94.
91. Mesters RM, Padro T, Bieker R, et al. Stable remission after administration of the receptor tyrosine kinase inhibitor SU5416 in a patient with refractory acute myeloid leukemia. Blood. 2001;98:241-243.
92. Minami Y, Kiyoi H, Yamamoto Y, et al. Selective apoptosis of tandemly duplicated FLT3-transformed leukemia cells by Hsp90 inhibitors. Leukemia. 2002;16:1535-1540.
93. Minami Y, Yamamoto K, Kiyoi H, Ueda R, Saito H, Naoe T. Different antiapoptotic pathways between wild-type and mutated FLT3: insights into therapeutic targets in leukemia. Blood. 2003;102:2969-2975.
94. Mizuki M, Fenski R, Halfter H, et al. Flt3 mutations from patients with acute myeloid leukemia induce transformation of 32D cells mediated by the Ras and STAT5 pathways. Blood. 2000;96:3907-3914.
95. Mizuki M, Schwable J, Steur C, et al. Suppression of myeloid transcription factors and induction of STAT response genes by AML-specific Flt3 mutations. Blood. 2003;101: 3164-3173.
96. Mizuki M, Schwaeble J, Steur C, et al. Suppression of myeloid transcription factors and induction of STAT response genes by AML-specific Flt3 mutations. Blood. 2003;101(8):3164-3173.
97. Moore TA, Zlotnik A. Differential effects of Flk-2/Flt-3 ligand and stem cell factor on murine thymic progenitor cells. J Immunol. 1997;158:4187-4192.
98. Morgan MA, Dolp O, Reuter CW. Cell-cycle-dependent activation of mitogen-activated protein kinase kinase (MEK-1/2) in myeloid leukemia cell lines and induction of growth inhibition and apoptosis by inhibitors of RAS signaling. Blood. 2001;97:1823-1834.
99. Murray LJ,Young JC,Osborne LJ, LuensKM, Scollay R, Hill BL. Thrombopoietin, flt3, and kit ligands together suppress apoptosis of human mobilized CD34+cells and recruit primitive CD34+ Thy-1+ cells into rapid division. Exp Hematol. 1999;27:1019-1028.
100. NakagawaT, Saitoh S, Imoto S, et al.Multiple point mutation of N-ras andK-ras oncogenes in myelodysplastic syndrome and acute myelogenous leukemia. Oncology. 1992;49:114-122.
101. Nakao M, Yokota S, Iwai T, et al. Internal tandem duplication of the flt3 gene found in acute myeloid leukemia. Leukemia. 1996;10:1911-1918.
102. Namikawa R, Muench MO, de Vries JE, Roncarolo MG. The FLK2/FLT3 ligand synergizes with interleukin-7 in promoting stromal-cell-independent expansion and differentiation of human fetal pro-B cells in vitro. Blood. 1996;87:1881-1890.
103. Nanri T, Matsuno N, Kawakita T, et al. Mutations in the receptor tyrosine kinase pathway are associated with clinical outcome in patients with acute myeloblastic leukemia harboring t(8;21)(q22;q22). Leukemia. 2005;19:1361-1366.
104. Neubauer A, Dodge RK, George SL, et al. Prognostic importance of mutations in the ras proto-oncogenes in de novo acute myeloid leukemia. Blood. 1994;83:1603-1611.
105. OFarrell AM, Abrams TJ, Yuen HA, et al. SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood. 2003;101:3597-3605.
106. OHare 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;65:4500-4505.
107. Oliff A. Farnesyltransferase inhibitors: targeting the molecular basis of cancer. Biochimica et Biophysica Acta. 1999;1423:C19-30.
108. Ouyang B, Knauf JA, Smith EP, et al. Inhibitors of Raf kinase activity block growth of thyroid cancer cells with RET/PTC or BRAF mutations in vitro and in vivo. Clin Cancer Res. 2006;12:1785-1793.
109. Padua RA, Guinn BA, Al-Sabah AI, et al. RAS, FMS and p53 mutations and poor clinical outcome in myelodysplasias: a 10-year follow-up. Leukemia. 1998;12:887-892.
110. Panka DJ, Wang W, Atkins MB, Mier JW. The Raf inhibitor BAY 43-9006 (Sorafenib) induces caspase-independent apoptosis in melanoma cells. Cancer Res. 2006;66:1611-1619.
111. Pellegata NS, Sessa F, Renault B, et al. K-ras and p53 gene mutations in pancreatic cancer: ductal and nonductal tumors progress through different genetic lesions. Cancer Res. 1994;54:1556-1560.
112. Prendergast GC, Davide JP, deSolms SJ, et al. Farnesyltransferase inhibition causes morphological reversion of ras-transformed cells by a complex mechanism that involves regulation of the actin cytoskeleton. Mol Cell Biol. 1994;14:4193-4202.
113. Radich JP, Kopecky KJ, Willman CL, et al. N-ras mutations in adult de novo acute myelogenous leukemia: prevalence and clinical significance. Blood. 1990;76: 801-807.
114. Rahmani M, Davis EM, Bauer C, Dent P, Grant S. Apoptosis induced by the kinase inhibitor BAY 43-9006 in human leukemia cells involves down-regulation of Mcl-1 through inhibition of translation. J Biol Chem. 2005;280:35217-35227.
115. Ray RJ, Paige CJ, Furlonger C, Lyman SD, Rottapel R. Flt3 ligand supports the differentiation of early B cell progenitors in the presence of interleukin-11 and interleukin. Eur J Immunol. 1996;26:1504-1510.
116. Reindl C, Bagrintseva K, Vempati S, et al. Point mutations found in the juxtamembrane domain of FLT3 define a new class of activating mutations in AML. Blood. 2006.
117. Ridge SA, Worwood M, Oscier D, Jacobs A, Padua RA. FMS mutations in myelodysplastic, leukemic, and normal subjects. Proc Natl Acad Sci USA. 1990;87:1377-1380.
118. Ridge SA, Worwood M, Oscier D, Jacobs A, Padua RA. FMS mutations in myelodysplastic, leukemic, and normal subjects. Proc Natl Acad Sci USA. 1990;87:1377-1380.
119. Ritter M, Kim TD, Lisske P, Thiede C, Schaich M, Neubauer A. Prognostic significance of N-RAS and K-RAS mutations in 232 patients with acute myeloid leukemia. Haematologica. 2004;89:1397-1399.
120. Robinson DR, Wu YM, Lin SF. The protein tyrosine kinase family of the human genome. Oncogene. 2000;19:5548-5557.
121. Rodenhuis S, van de Wetering ML, Mooi WJ, Evers SG, van Zandwijk N, Bos JL. Mutational activation of the K-ras oncogene. A possible pathogenetic factor in adenocarcinoma of the lung. N Engl J Med. 1987;317:929-935.
122. Rosenbauer F, Wagner K, Kutok JL, et al. Acute myeloid leukemia induced by graded reduction of a lineage-specific transcription factor, PU.1. Nat Genet. 2004;36:624-630.
123. Roskoski R, Jr. Structure and regulation of Kit protein-tyrosine kinase-the stem cell factor receptor. Biochem Biophys Res Commun. 2005;338:1307-1315.
124. Rosnet O, Birnbaum D. Hematopoietic receptors of class III receptor-type tyrosine kinases. Crit Rev Oncog. 1993;4:595-613.
125. Roussel MF, Downing JR, Rettenmier CW, Sherr CJ. A point mutation in the extracellular domain of the human CSF-1 receptor (c-fms proto-oncogene product) activates its transforming potential. Cell. 1988;55:979-988.
126. Rusten LS, Lyman SD, Veiby OP, Jacobsen SE. The FLT3 ligand is a direct and potent stimulator of the growth of primitive and committed human CD34+ bone marrow progenitor cells in vitro. Blood. 1996;87:1317-1325.
127. Schessl C, Rawat VP, Cusan M, et al. The AML1-ETO fusion gene and the FLT3 length mutation collaborate in inducing acute leukemia in mice. J Clin Invest. 2005;115: 2159-2168.
128. Schittenhelm MM, Shiraga S, Schroeder A, et al. Dasatinib (BMS-354825), a dual SRC/ ABL kinase inhibitor, inhibits the kinase activity of wild-type, juxtamembrane, and activation loop mutant KIT isoforms associated with human malignancies. Cancer Res. 2006;66:473-481.
129. Schnittger S, Kohl TM, Haferlach T, et al. KIT-D816 mutations in AML1-ETOpositive AML are associated with impaired event-free and overall survival. Blood. 2006;107: 1791-1799.
130. Schnittger S, Schoch C, Dugas M, et al. Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease. Blood. 2002;100:59-66.
131. Sebti SM, Der CJ. Opinion: searching for the elusive targets of farnesyltransferase inhibitors. Nat Rev Cancer. 2003;3:945-951.
132. SEER Cancer Statistics Review 1975-2001, Vol.2004. National Cancer Institute; 2004. http://seer.cancer.gov/csr/1975-2004/. Accessed on 15 July, 2009.
133. Shah AJ, Smogorzewska EM, Hannum C, Crooks GM. Flt3 ligand induces proliferation of quiescent human bone marrow CD34+CD38- cells and maintains progenitor cells in vitro. Blood. 1996;87:3563-3570.
134. Shimada A, Taki T, Tabuchi K, et al. KIT mutations, and not FLT3 internal tandem duplication, are strongly associated with a poor prognosis in pediatric acute myeloid leukemia with t(8;21): a study of the Japanese Childhood AML Cooperative Study Group. Blood. 2006;107:1806-1809.
135. Slebos RJ, Kibbelaar RE, Dalesio O, et al. K-ras oncogene activation as a prognostic marker in adenocarcinoma of the lung. N Engl J Med. 1990;323:561-565.
136. Smith BD, Levis M, Beran M, et al. Single-agent CEP-701, a novel FLT3 inhibitor, shows biologic and clinical activity in patients with relapsed or refractory acute myeloid leukemia. Blood. 2004;103:3669-3676.
137. Smith BD, Levis M, Brown P, et al. Single agent CEP-701, a novel FLT-3 inhibitor, shows initial response in patients with refractory acute myeloid leukemia. Blood. 2002;100:314a.
138. Smith ML, Snadden J, Neat M, et al. Mutation of BRAF is uncommon in AML FAB type M1 and M2. Leukemia. 2003;17:274-275.
139. Smolich BD, Yuen HA, West KA, Giles FJ, Albitar M, Cherrington JM. The antiangiogenic protein kinase inhibitors SU5416 and SU6668 inhibit the SCF receptor (c-kit) in a human myeloid leukemia cell line and in acute myeloid leukemia blasts. Blood. 2001;97:1413-1421.
140. Spiekermann K, Bagrintseva K, Schoch C, Haferlach T, Hiddemann W, Schnittger S. A new and recurrent activating length mutation in exon 20 of the FLT3 gene in acute myeloid leukemia. Blood. 2002;100:3423-3425.
141. Springall F, OMara S, Shounan Y, Todd A, Ford D, Iland H. c-fms point mutations in acute myeloid leukemia: fact or fiction? Leukemia. 1993;7:978-985.
142. Sridhar SS, Hedley D, Siu LL. Raf kinase as a target for anticancer therapeutics. Mol Cancer Ther. 2005;4:677-685.
143. Stephenson SA, Slomka S, Douglas EL, Hewett PJ, Hardingham JE. Receptor protein tyrosine kinase EphB4 is up-regulated in colon cancer. BMC Mol Biol. 2001;2:15.
144. Stirewalt DL, Kopecky KJ, Meshinchi S, et al. FLT3, RAS, and TP53 mutations in elderly patients with acute myeloid leukemia. Blood. 2001;97:3589-3595.
145. Stirewalt DL, Kopecky KJ, Meshinchi S, et al. Size of FLT3 internal tandem duplication has prognostic significance in patients with acute myeloid leukemia. Blood. 2006;107: 3724-3726.
146. Stirewalt DL, Meshinchi S, Kussick SJ, et al. Novel FLT3 point mutations within exon 14 found in patients with acute myeloid leukaemia. Br J Haematol. 2004;124:481-484.
147. Stirewalt DL, Radich JP. The role of FLT3 in haematopoietic malignancies. Nat Rev Cancer. 2003;3:650-665.
148. Stone RM, DeAngelo DJ, Klimek V, et al. Patients with acute myeloid leukemia and an activating mutation in FLT3 respond to a small-molecule FLT3 tyrosine kinase inhibitor, PKC412. Blood. 2005;105:54-60.
149. Stone RM, Fischer T, Paquette R, et al. Phase 1B study of PKC412, an oral FLT3 kinase inhibitor, in sequential and simultaneous combinations with daunorubicin and cytarabine (DA) induction and high-dose consolidation in newly diagnosed patients with AML. Blood. 2005;106:404a.
150. StoneRM,Klimek V, J.DD, et al. PKC412, an oral FLT3 inhibitor, has activity inmutant FLT3 acute myeloid leukemia (AML): a phase II clinical trial. Blood. 2002;100:316a.
151. Tartaglia M, Martinelli S, Iavarone I, et al. Somatic PTPN11 mutations in childhood acute myeloid leukaemia. Br J Haematol. 2005;129:333-339.
152. Thiede C, Steudel C, Mohr B, et al. Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood. 2002;99:4326-4335.
153. Tobal K, Pagliuca A, Bhatt B, Bailey N, Layton DM, Mufti GJ. Mutation of the human FMS gene (M-CSF receptor) in myelodysplastic syndromes and acute myeloid leukemia. Leukemia. 1990;4:486-489.
154. Tomasson MH, Sternberg DW, Williams IR, et al. Fatal myeloproliferation, induced in mice by TEL/PDGFbetaR expression, depends on PDGFbetaR tyrosines 579/581. J Clin Invest. 2000;105:423-432.
155. Tomasson MH, Williams IR, Hasserjian R, et al. TEL/PDGFbetaR induces hematologic malignancies in mice that respond to a specific tyrosine kinase inhibitor. Blood. 1999;93:1707-1714.
156. Tong FK, Chow S, Hedley D. Pharmacodynamic monitoring of BAY 43-9006 (Sorafenib) in phase I clinical trials involving solid tumor and AML/MDS patients, using flow cytometry to monitor activation of the ERK pathway in peripheral blood cells. Cytometry B Clin Cytom. 2006;70(3):107-114.
157. Towatari M, Iida H, Tanimoto M, Iwata H, Hamaguchi M, Saito H. Constitutive activation of mitogen-activated protein kinase pathway in acute leukemia cells. Leukemia. 1997;11:479-484.
158. Tse KF, Allebach J, Levis M, Smith BD, Bohmer FD, Small D. Inhibition of the transforming activity of FLT3 internal tandem duplication mutants from AML patients by a tyrosine kinase inhibitor. Leukemia. 2002;16:2027-2036.
159. Tse KF, Mukherjee G, Small D. Constitutive activation of FLT3 stimulates multiple intracellular signal transducers and results in transformation. Leukemia. 2000;14: 1766-1776.
160. Tsujimura T, Furitsu T, Morimoto M, et al. Ligand-independent activation of c-kit receptor tyrosine kinase in a murine mastocytoma cell line P-815 generated by a point mutation. Blood. 1994;83:2619-2626.
161. Tsujimura T, Kanakura Y, Kitamura Y. Mechanisms of constitutive activation of c-kit receptor tyrosine kinase. Leukemia. 1997;11 Suppl 3:396-398.
162. Tsujimura T, Morimoto M, Hashimoto K, et al. Constitutive activation of c-kit in FMA3 murine mastocytoma cells caused by deletion of seven amino acids at the juxtamembrane domain. Blood. 1996;87:273-283.
163. Turner AM, Lin NL, Issarachai S, Lyman SD, Broudy VC. FLT3 receptor expression on the surface of normal and malignant human hematopoietic cells. Blood. 1996;88: 3383-3390.
164. Ueda S, Ikeda H, Mizuki M, et al. Constitutive activation of c-kit by the juxtamembrane but not the catalytic domain mutations is inhibited selectively by tyrosine kinase inhibitors STI571 and AG1296. Int J Hematol. 2002;76:427-435.
165. van der Geer P, Hunter T. Identification of tyrosine 706 in the kinase insert as the major colony-stimulating factor 1 (CSF-1)-stimulated autophosphorylation site in the CSF-1 receptor in a murine macrophage cell line. Mol Cell Biol. 1990;10:2991-3002.
166. Vandenberghe P, Wlodarska I, Michaux L, et al. Clinical and molecular features of FIP1L1-PDFGRA (+) chronic eosinophilic leukemias. Leukemia. 2004;18:734-742.
167. Veiby OP, Lyman SD, Jacobsen SE. Combined signaling through interleukin-7 receptors and flt3 but not c-kit potently and selectively promotes B-cell commitment and differentiation from uncommitted murine bone marrow progenitor cells. Blood. 1996;88: 1256-1265.
168. Vogelstein B, Civin CI, Preisinger AC, et al. RAS gene mutations in childhood acute myeloid leukemia: a Pediatric Oncology Group study. Genes Chromosomes Cancer. 1990;2:159-162.
169. Wallace EM, Lyssikatos J, Blake JF, et al. Potent and selective mitogen-activated protein kinase kinase (MEK) 1,2 inhibitors. 1. 4-(4-bromo-2-fluorophenylamino)-1-methylpyridin-2(1H)-ones. J Med Chem. 2006;49:441-444.
170. Wang YY, Zhou GB, Yin T, et al. AML1-ETO and C-KIT mutation/ overexpression in t(8;21) leukemia: implication in stepwise leukemogenesis and response to Gleevec. Proc Natl Acad Sci USA. 2005;102:1104-1109.
171. Weiner HL, Zagzag D. Growth factor receptor tyrosine kinases: cell adhesion kinase family suggests a novel signaling mechanism in cancer. Cancer Invest. 2000;18:544-554.
172. Weisberg E, Boulton C, Kelly LM, et al. Inhibition of mutant FLT3 receptors in leukemia cells by the small molecule tyrosine kinase inhibitor PKC412. Cancer Cell. 2002;1:433-443.
173. Whitman SP, Archer KJ, Feng L, et al. Absence of the wild-type allele predicts poor prognosis in adult de novo acute myeloid leukemia with normal cytogenetics and the internal tandem duplication of FLT3: a cancer and leukemia group B study. Cancer Res. 2001;61:7233-7239.
174. Wiener JR, Kassim SK, Yu Y, Mills GB, Bast RC, Jr. Transfection of human ovarian cancer cells with the HER-2/neu receptor tyrosine kinase induces a selective increase in PTP-H1, PTP-1B, PTP-alpha expression. Gynecol Oncol. 1996;61:233-240.
175. Yamamoto Y, Kiyoi H, Nakano Y, et al. Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies. Blood. 2001;97:2434-2439.
176. Yamashita N, Osato M, Huang L, et al. Haploinsufficiency of Runx1/AML1 promotes myeloid features and leukaemogenesis in BXH2 mice. Br J Haematol. 2005;131:495-507.
177. Yee KW, OFarrell AM, Smolich BD, et al. SU5416 and SU5614 inhibit kinase activity of wild-type and mutant FLT3 receptor tyrosine kinase. Blood. 2002;100:2941-2949.
178. Yee NS, Langen H, Besmer P. Mechanism of kit ligand, phorbol ester, and calciuminduced down-regulation of c-kit receptors in mast cells. J Biol Chem. 1993;268:14189-14201.
179. Yokota S, Kiyoi H, Nakao M, et al. Internal tandem duplication of the FLT3 gene is preferentially seen in acute myeloid leukemia and myelodysplastic syndrome among various hematological malignancies. A study on a large series of patients and cell lines. Leukemia. 1997;11:1605-1609.
180. Zhao M, Kiyoi H, Yamamoto Y, et al. In vivo treatment of mutant FLT3-transformed murine leukemia with a tyrosine kinase inhibitor. Leukemia. 2000;14:374-378.
181. Zheng R, Levis M, Piloto O, et al. FLT3 ligand causes autocrine signaling in acute myeloid leukemia cells. Blood. 2004;103:267-274.
182. Zwaan CM, Meshinchi S, Radich JP, et al. FLT3 internal tandem duplication in 234 children with acute myeloid leukemia: prognostic significance and relation to cellular drug resistance. Blood. 2003;102:2387-2394.