C-KIT signaling in cancer treatment

Current Pharmaceutical Design

Volumn 20, Issue 17, 2014, Pages 2849-2880

  Stankov, Karmen ^a   Popovic, Stevan ^a   Mikov, Momir ^a  

^a UNIVERSITY OF NOVI SAD   (Serbia)

Author keywords

C KIT; Cancer; GIST; Leukemia; Mastocytosis; Melanoma; Therapy; Tyrosine kinases

Indexed keywords

BORTEZOMIB; CORE BINDING FACTOR; DASATINIB; HISTONE DEACETYLASE INHIBITOR; IMATINIB; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHOLIPASE C; PROTEIN TYROSINE KINASE; PROTEIN TYROSINE KINASE INHIBITOR; QUIZARTINIB; STEM CELL FACTOR; STEM CELL FACTOR RECEPTOR; SUPPRESSOR OF CYTOKINE SIGNALING; TYROSINE KINASE RECEPTOR; TYRPHOSTIN; PROTEIN KINASE INHIBITOR;

ACUTE GRANULOCYTIC LEUKEMIA; ALTERNATIVE RNA SPLICING; ANGIOGENESIS; APOPTOSIS; CANCER CHEMOTHERAPY; CANCER COMBINATION CHEMOTHERAPY; CANCER PROGNOSIS; CANCER RADIOTHERAPY; CANCER SURGERY; CELL ADHESION; CELL MOTILITY; CELL PROLIFERATION; CELL SURVIVAL; ETIOLOGY; GAIN OF FUNCTION MUTATION; GASTROINTESTINAL STROMAL TUMOR; GENE EXPRESSION PROFILING; HUMAN; LOSS OF FUNCTION MUTATION; MAST CELL LEUKEMIA; MASTOCYTOSIS; MELANOMA; MOLECULAR EPIDEMIOLOGY; MOLECULARLY TARGETED THERAPY; NONHUMAN; PATHOGENESIS; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; AGONISTS; ANTAGONISTS AND INHIBITORS; BIOLOGICAL MODEL; DRUG EFFECTS; GENETICS; METABOLISM; MUTATION; NEOPLASMS;

CELL PROLIFERATION; HUMANS; MODELS, BIOLOGICAL; MOLECULAR TARGETED THERAPY; MUTATION; NEOPLASMS; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-KIT; SIGNAL TRANSDUCTION;

EID: 84903709933     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/13816128113199990593     Document Type: Review

References (243)

1. Savonarola A, Palmirotta R, Guadagni F, Silvestris F. Pharmacogenetics and pharmacogenomics: role of mutational analysis in anti-cancer targeted therapy. Pharmacogenomics J 2012; 12: 277-286.
2. Lemmon MA, Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell 2010; 141: 1117-34.
3. Bennasroune A, Gardin A, Aunis D, Crémel G, Hubert P. Tyrosine kinase receptors as attractive targets of cancer therapy. Crit Rev Oncol Hematol 2004; 50: 23-38.
4. Ferrara F. New agents for acute myeloid leukemia: is it time for targeted therapies? Expert Opin Investig Drugs 2012; 21: 179-89.
5. Rosenzweig SA. Acquired resistance to drugs targeting receptor tyrosine kinases. Biochem Pharmacol 2012; 83: 1041-8.
6. Hao GF, Yang GF, Zhan CG. Structure-based methods for predicting target mutation-induced drug resistance and rational drug design to overcome the problem. Drug Discov Today 2012; 17: 1121-6.
7. Masson K, Rönnstrand L. Oncogenic signaling from the hematopoietic growth factor receptors c-Kit and Flt3. Cell Signal 2009; 21: 1717-26.
8. Pittoni P, Piconese S, Tripodo C, Colombo MP. Tumor-intrinsic and-extrinsic roles of c-kit: mast cells as the primary off target of tyrosine kinase inhibitors. Oncogene 2011; 30: 757-69
9. Rulina AV, Spirin PV, Prassolov VS. Activated leukemic oncogenes AML1-ETO and c-kit: role in development of acute myeloid leukemia and current approaches for their inhibition. Biochem Moscow 2010;75: 1650-66.
10. Mol CD, Lim KB, Sridhar V, et al. Structure of a c-kit product complex reveals the basis for kinase transactivation. J Biol Chem 2003; 278: 31461-4.
11. Roskoski R Jr. Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor. Biochem Biophys Res Commun 2005; 337: 1-13.
12. Lyman SD, Jacobsen SE. C-kit ligand and Flt3 ligand: stem/progenitor cell factors with overlapping yet distinct activities. Blood 1998; 91: 1101-34.
13. Montero JC, López-Pérez R, San Miguel JF, Pandiella A. Expression of c-Kit isoforms in multiple myeloma: differences in signaling and drug sensitivity. Haematologica 2008; 93: 851-9.
14. Pedersen M, Rönnstrand L, Sun J. The c-Kit/D816V mutation eliminates the differences in signal transduction and biological responses between two isoforms of c-Kit. Cell Signal 2009; 21: 413-8.
15. Voytyuk O, Lennartsson J, Mogi A, et al. Src family kinases are involved in the differential signaling from two splice forms of c-Kit. J Biol Chem 2003; 278: 9159-66.
16. Sakuma Y, Sakurai S, Oguni S, Hironaka M, Saito K. Alterations of the c-kit gene in testicular germ cell tumors. Cancer Sci 2003; 94: 486-91.
17. Kapur R, Chandra S, Cooper R, McCarthy J, Williams DA. Role of p38 and ERK MAPkinase in proliferation of erythroid progenitors in response to stimulation by soluble and membrane isoforms of stem cell factor. Blood 2002; 100: 1287-93.
18. Lennartson J, Voytyuk O, Heiss E, Sundberg C, Sun J, Ronnstrand L. C-kit signal transduction and involvement in cancer. Cancer Ther 2005; 3: 5-28
19. Anderson DM, Lyman SD, Baird A, et al. Molecular cloning of mast cell growth factor, a hematopoietin that is active in both membrane bound and soluble forms. Cell 1990; 63: 235-43.
20. Palmqvist L, Glover CH, Hsu L, et al. Correlation of murine embryonic stem cell gene expression profiles with functional measures of pluripotency. Stem Cells 2005; 23: 663-80.
21. Takagi S, Saito Y, Hijikata A, et al. Membrane-bound human SCF/KL promotes in vivo human hematopoietic engraftment and myeloid differentiation. Blood 2012; 119: 2768-77.
22. Zhu HH, Ji K, Alderson N, et al. Kit-Shp2-Kit signaling acts to maintain a functional hematopoietic stem and progenitor cell pool. Blood 2011; 117: 5350-61.
23. Liu H, Chen X, Focia PJ, He X. Structural basis for stem cell factor-KIT signaling and activation of class III receptor tyrosine kinases. EMBO J 2007; 26: 891-901.
24. Yuzawa S, Opatowsky Y, Zhang Z, Mandiyan V, Lax I, Schlessinger J. Structural basis for activation of the receptor tyrosine kinase KIT by stem cell factor. Cell 2007; 130: 323-34.
25. Toffalini F, Demoulin JB. New insights into the mechanisms of hematopoietic cell transformation by activated receptor tyrosine kinases. Blood 2010; 116: 2429-37.
26. Masson K, Heiss E, Band H, Rönnstrand L. Direct binding of Cbl to Tyr568 and Tyr936 of the stem cell factor receptor/c-Kit is required for ligand-induced ubiquitination, internalization and degradation. Biochem J 2006; 399: 59-67.
27. Lai RH, Hsiao YW, Wang MJ, et al. SOCS6, down-regulated in gastric cancer, inhibits cell proliferation and colony formation. Cancer Lett 2010; 288: 75-85
28. Bayle J, Letard S, Frank R, Dubreuil P, De Sepulveda P. Suppressor of Cytokine Signaling 6 Associates with KIT and Regulates KIT Receptor Signaling. J Biol Chem 2004; 279: 12249-59.
29. Zadjali F, Pike AC, Vesterlund M, et al. Structural basis for c-KIT inhibition by the suppressor of c cytokine signaling 6 (SOCS6) ubiquitin ligase. J Biol Chem 2011; 286: 480-90.
30. Corless CL, Barnett CM, Heinrich MC. Gastrointestinal stromal tumours: origin and molecular oncology. Nat Rev Cancer 2011; 11: 865-78.
31. Bauer S, Yu LK, Demetri GD, Fletcher JA. Heat shock protein 90 inhibition in imatinib-resistant gastrointestinal stromal tumor. Cancer Res 2006; 66: 9153-61.
32. Russel ES. Hereditary anemias of the mouse: a review for geneticists. Adv Genet 1979; 20: 357-459
33. Besmer P, Murphy JE, George PC, et al. A new acute transforming feline retrovirus and relationship of its oncogene v-kit with the protein kinase gene family. Nature 1986; 320: 415-21.
34. Nocka K, Majumder S, Chabot B, et al. pression of c-kit gene products in known cellular targets of W mutations in normal and W mutant mice-evidence for an impaired c-kit kinase in mutant mice. Genes Dev 1989; 3: 816-26.
35. Majumder S, Brown K, Qiu FH, Besmer P. c-kit protein, a transmembrane kinase: identification in tissues and characterization. Mol Cell Biol 1988; 8: 4896-903.
36. Chabot B, Stephenson DA, Chapman VM, Besmer P, Bernstein A. The proto-oncogene c-kit encoding a transmembrane tyrosine kinase receptor maps to the mouse W locus. Nature 1988; 335: 88-9.
37. Geissler EN, Ryan MA, Housman DE. The dominant-white spotting (W) locus of the mouse encodes the c-kit proto-oncogene. Cell 1988; 55: 185-92.
38. Zsebo KM, Williams DA, Geissler EN, Broudy VC, Martin FH, Atkins HL. Stem cell factor is encoded at the Sl locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor. Cell 1990; 63: 213-24
39. Gadd SJ, Ashman LK. A murine monoclonal antibody specific for a cell-surface antigen expressed by a subgroup of human myeloid leukaemias. Leuk Res 1985; 9: 1329-36
40. Rönnstrand L. Signal transduction via the stem cell factor receptor/ c-Kit. Cell Mol Life Sci 2004; 61: 2535-48.
41. Huang E, Nocka K, Beier DR, et al. The hematopoietic growth factor KL is encoded by the Sl locus and is the ligand of the c-kit receptor, the gene product of the W locus. Cell 1990; 63: 225-33.
42. Martin FH, Suggs SV, Langley KE, et al. Primary structure and functional expression of rat and human stem cell factor DNAs. Cell 1990; 63: 203-11.
43. Williams DE, Eisenman J, Baird A, et al. Identification of a ligand for the c-kit proto-oncogene. Cell 1990; 63: 167-74.
44. Sattler M, Salgia R. Targeting c-kit mutations: basic science to novel therapies. Leukemia Res 2004; 28S1: S11-S20
45. Fleischman RA, Gallardo T, Mi X. Mutations in the ligand-binding domain of the kit receptor: an uncommon site in human piebaldism. J Invest Dermatol 1996; 107: 703-6.
46. Murakami T, Fukai K, Oiso N, et al. New KIT mutations in patients with piebaldism. J Dermatol Sci 2004; 35: 29-33.
47. Corless CL, Heinrich MC. Molecular pathobiology of gastrointestinal stromal sarcomas. Annu Rev Pathol 2008; 3: 557-86.
48. Orinska Z, Foger N, Huber M, et al. I787 provides signals for c-Kit receptor internalization and functionality that control mast cell survival and development. Blood 2010; 116: 2665-75.
49. Maddens S, Charruyer A, Plo I, et al. Kit signaling inhibits the sphingomyelin-ceramide pathway through PLC#1: implication in stem cell factor radioprotective effect. Blood 2002; 100: 1294-301.
50. Scheijen B, Griffin JD. Tyrosine kinase oncogenes in normal hematopoiesis and hematological disease. Oncogene 2002; 21: 3314-33.
51. Vivanco I, Sawyers CL. The phosphatidylinositol 3-Kinase-AKT pathway in human cancer. Nat Rev Cancer 2002; 2: 489-501.
52. Wandzioch E, Edling C, Pulmer R, Carisson L, Hallberg B. Activation of the MAP kinase pathway by c-Kit is PI-3 kinase dependent in hematopoietic progenitor/stem cell lines. Blood 2004; 104: 51-7.
53. Steelman LS, Chappell WH, Abrams SL, et al. Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging. Aging 2011; 3: 192-222.
54. Abdeli S, Bonny C. Akt acts through a wide array of downstream protein substrates involved in apoptosis, mitogenesis, cell proliferation and survival. PLoS One 2012; 7: e35997.
55. Sykes SM, Lane SW, Bullinger L, et al. AKT/FOXO signaling enforces reversible differentiation blockade in myeloid leukemias. Cell 2011; 146: 697-708.
56. Tzivion G, Dobson M, Ramakrishnan G. FoxO transcription factors; Regulation by AKT and 14-3-3 proteins. Biochim Biophys Acta 2011; 1813: 1938-45
57. Kishimoto H, Hamada K, Saunders M, et al. Physiological functions of Pten in mouse tissues. Cell Struct Funct 2003; 28: 11-21
58. Chian R, Young S, Danilkovitch-Miagkova A, et al. Phosphatidylinositol 3 kinase contributes to the transformation of hematopoietic cells by the D816V c-Kit mutant. Blood 2001; 98: 1365-73.
59. Sun J, Pedersen M, Rönnstrand L. Gab2 is involved in differential phosphoinositide 3-kinase signaling by two splice forms of c-Kit. J Biol Chem 2008; 283: 27444-51.
60. Edling CE, Hallberg B. C-Kit-A hematopoietic cell essential receptor tyrosine kinase. Int J Biochem Cell Biol 2007; 39: 1995-8.
61. Tetsu O, Phuchareon J, Chou A, Cox DP, Eisele DW, Jordan RC. Mutations in the c-Kit gene disrupt mitogen-activated protein kinase signaling during tumor development in adenoid cystic carcinoma of the salivary glands. Neoplasia 2010; 12: 708-17.
62. Shaul YD, Seger R. The MEK/ERK cascade: from signaling specificity to diverse functions. Biochim Biophys Acta 2007; 1773: 1213-26.
63. Roberts PJ, Der CJ. Targeting the Raf-MEK-ERK mitogenactivated protein kinase cascade for the treatment of cancer. Oncogene 2007; 26: 3291-310.
64. Guida T, Anaganti S, Provitera L, et al. Sorafenib Inhibits Imatinib-Resistant KIT and Platelet-Derived Growth Factor Receptor $ Gatekeeper Mutants. Clin Cancer Res 2007; 13: 3363-9.
65. Diel U, Oztuzcu S, Been AA, et al. Promising efficacy of sorafenib in a relapsed thymic carcinoma with C-KIT exon 11 deletion mutation. Lung Cancer 2011; 71: 109-12.
66. Wilhelm SM, Carter C, Tang L, et al. BAY 43-9006 exhibits broad spectrum of antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 2004; 64: 7099-109.
67. Heikki J. Adjuvant treatment of GIST: patient selection and treatment strategies. Nat Rev Clin Oncol 2012; 9: 351-8
68. Lai ECH, Lau SHY, Lau WY. Current management of gastrointestinal stromal tumors-A comprehensive review. Int J Surg 2012; 10: 334-40.
69. DeMatteo RP, Heinrich MC, el-Rifai W, Demetri G. Clinical management of gastrointestinal stromal tumors: Before and after STI-571. Hum Pathol 2002; 33: 466-77.
70. Liegl-Atzwanger B, Fletcher JA, Fletcher CDM. Gastrointestinal stromal tumors. Virchows Arch 2010; 456: 111-27.
71. Hirota S, Isozaki K, Moriyama Y, et al. Gain of function mutations of c-kit in human gastrointestinal stromal tumors. Science 1998; 279: 577-80.
72. Maleddu A, Pantaleo MA, Nannini M, Biasco G. The role of mutational analysis of KIT and PDGFR in gastrointestinal stromal tumors in a clinical setting. J Transl Med 2011; 9: 75.
73. Tornillo L, Terracciano LM. An update on molecular genetics of gastrointestinal stromal tumours. J Clin Pathol 2006; 59: 557-63.
74. Miranda C, Nucifora M, Molinari F, et al. KRAS and BRAF Mutations Predict Primary Resistance to Imatinib in Gastrointestinal Stromal Tumors. Clin Cancer Res 2012; 18; 1769-76.
75. Lopes LF, Bacchi CE. Imatinib treatment of gastrointestinal stromal tumors. J Cell Mol Med 2010; 14: 42-50.
76. Agaimy A, Terracciano LM, Dirnhofer S, et al. V600E BRAF mutations are alternative early molecular events in a subset of KIT/PDGFRA wild-type gastrointestinal stromal tumours. J Clin Pathol 2009; 62: 613-16.
77. Pantaleo MA, Astolfi A, Indio V, et al. SDHA loss-of-function mutations in KIT-PDGFRA wild-type gastrointestinal stromal tumors identified by massively parallel sequencing. J Natl Cancer Inst 2011; 103: 983-7.
78. Rubin BP, Antonescu CR, Scott-Browne JP, Comstock ML, Gu Y, Tanas MR, Ware CB, Woodell J. A knock-in mouse model of gastrointestinal stromal tumor harboring kit K641E. Cancer Res 2005; 65: 6631-9.
79. Mol CD, Dougan DR, Schneider TR, et al. Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase. J Biol Chem 2004; 279: 31655-63.
80. Joensuu H. Adjuvant treatment of GIST: patient selection and treatment strategies. Nat Rev Clin Oncol 2012; 9: 351-8.
81. Antonescu CR. Targeted therapy of cancer: new roles for pathologists in identifying GISTs and other sarcomas. Modern Pathol 2008; 21: S31-36.
82. Antonescu CR, Viale A, Sarran L, et al. Gene expression in gastrointestinal stromal tumors is distinguished by KIT genotype and anatomic site. Clin Cancer Res 2004; 10: 3282-90.
83. Rutkowski P, Badalamenti G, La Paglia L, Przybyl J, Debiec-Rychter M. Gene signatures in Gastrointestinal Stomal Tumors. In: Russo A, Iacobelli S, Iovanna J. Diagnostic, Prognostic and Therapeutic Value of Gene Signatures. Current Clinical Pathology. Springer Science + Business Media, LLC 2012; pp 35-50.
84. Ostrowski J, Polkowski M, Paziewska A, et al. Functional features of gene expression profiles differentiating gastrointestinal stromal tumours according to KIT mutations and expression. BMC Cancer 2009; 9: 413.
85. Kim WK, Park M, Kim YK, et al. MicroRNA-494 downregulates KIT and inhibits gastrointestinal stromal tumor cell proliferation. Clin Cancer Res 2011; 17: 7584-94.
86. Xiang Z, Kreisel F, Cain J, Colson A, Tomasson MH. Neoplasia driven by mutant c-KIT is mediated by intracellular, not plasma membrane, receptor signaling. Mol Cell Biol 2007;27: 267-82.
87. Lee HE, Kim MA, Lee HS, Lee BL, Kim WH. Characteristics of KIT-negative gastrointestinal stromal tumours and diagnostic utility of protein kinase C theta immunostaining. J Clin Pathol 2008; 61: 722-9.
88. Nannini M, Biasco G, Maleddu A, Pantaleo MA. New molecular targets beyond KIT and PDGFRA in gastrointestinal stromal tumors: present and future. Expert Opin Ther Targets 2011; 15: 803-15.
89. Daum O, Vanecek T, Benes Z, Michal M. Progress in molecular diagnostics of gastrointestinal stromal tumors. Expert Opin Med Diagn 2007; 1: 315-24.
90. Daniels M, Lurkin I, Pauli R, et al. Spectrum of KIT/PDGFRA/BRAF mutations and Phosphatidylinositol-3-Kinase pathway gene alterations in gastrointestinal stromal tumors (GIST). Cancer Lett 2011;312:43-54.
91. Bauer S, Duensing A, Demetri GD, Fletcher JA. T oncogenic signaling mechanisms in imatinib-resistant gastrointestinal stromal tumor: PI3-kinase/AKT is a crucial survival pathway. Oncogene 2007; 26: 7560-8.
92. Engleman JA, Luo J, Cantley LC. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Cancer 2006; 7: 606-19.
93. Koshenkov VP, Rogders SE. Adjuvant therapy of gastrointestinal stromal tumors. Curr Opin Oncol 2012; 24: 414-8.
94. Fabbro D, Cowan-Jacob SW, Möbitz H, Martiny-Baron G. Targeting cancer with small-molecular-weight kinase inhibitors. Methods Mol Biol 2012; 795: 1-34.
95. Joensuu H, Eriksson M, Sundby Hall K, et al. One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial. JAMA 2012; 307: 1265-72.
96. von Mehren M. The role of adjuvant and neoadjuvant therapy in gastrointestinal stromal tumors. Curr Opin Oncol 2008; 20: 428-32
97. Schmidt C. FDA updates Gleevec label for GIST patients. J Natl Cancer Inst 2012; 104: 346.
98. Pierotti MA, Tamborini E, Negri T, Pricl S, Pilotti S. Targeted therapy in GIST: in silico modeling for prediction of resistance. Nat Rev Clin Oncol 2011; 8: 161-70.
99. Marrari A, Trent JC, George S. Personalized cancer therapy for gastrointestinal stromal tumor: synergizing tumor genotyping with imatinib plasma levels. Curr Opin Oncol 2010; 22: 336-41.
100. Pantaleo MA, Nannini M, Di Battista M, Catena F, Biasco G. Combined treatment strategies in gastrointestinal stromal tumors (GISTs) after imatinib and sunitinib therapy. Cancer Treat Rev 2010;36: 63-8.
101. Blay J-Y: Pharmacological management of gastrointestinal stromal tumours: an update on the role of sunitinib. Ann Oncol 2010; 21: 208-15.
102. Demetri GD, van Oosterom AT, Garrett CR, et al Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: A randomised controlled trial. Lancet 2006; 368: 1329-38.
103. Rutkowski P, Bylina E, Klimczak A, et al. The outcome and predictive factors of sunitinib therapy in advanced gastrointestinal stromal tumors (GIST) after imatinib failure-one institution study. BMC Cancer 2012;12:107.
104. Blay JY, Demetri GD. The evolution of a revolutionary class: extending benefits of tyrosine kinase inhibitors--introduction. Semin Oncol 2011;38: S1-2.
105. Blay JY, von Mehren M. Nilotinib: a novel, selective tyrosine kinase inhibitor. Semin Oncol 2011; 38: S3-9
106. Strumberg D, Schultheis B. Regorafenib for cancer. Expert Opin Investig Drugs 2012; 21: 879-89.
107. Bauer S, Parry JA, Mühlenberg T, et al. Proapoptotic activity of bortezomib in gastrointestinal stromal tumor cells. Cancer Res 2010; 70: 150-9.
108. Felli N, Fontana L, Pelosi E, Botta R, Bonci D, Facchiano F. MicroRNAs 221 and 222 inhibit normal erythropoiesis and erythroleukemic cell growth via kit receptor down-modulation. Proc Natl Acad Sci USA 2005; 102: 18081-6.
109. Muhlenberg T, Zhang Y, Wagner AJ et al. Inhibitors of deacetylases suppress oncogenic KIT signaling, acetylate HSP90, and induce apoptosis in gastrointestinal stromal tumors. Cancer Res 2009; 69: 6941-50.
110. Romano E, Schwartz GK, Chapman PB, Wolchock JD, Carvajal RD. Treatment implications of the emerging molecular classification system for melanoma. Lancet Oncol 2011; 12: 913-22.
111. van den Hurk K, Niessen HE, Veeck J, et al. Genetics and epigenetics of cutaneous malignant melanoma: A concert out of tune. Biochim Biophys Acta 2012; 1826: 89-102.
112. Law MH, Macgregor S, Hayward NK. Melanoma genetics: Recent findings take us beyond well-traveled pathways. J Invest Dermatol 2012; 132: 1763-74
113. Goldstein AM, Chan M, Harland M, et al; Lund Melanoma Study Group; Melanoma Genetics Consortium (GenoMEL). Features associated with germline CDKN2A mutations: a GenoMEL study of melanoma-prone families from three continents. J Med Genet 2007;44: 99-106.
114. Wiesner T, Obenauf AC, Murali R, et al. Germline mutations in BAP1 predispose to melanocytic tumors. Nat Genet 2011; 43: 1018-21.
115. Miller AJ, Mihm MC Jr. Melanoma. N Engl J Med 2006; 355: 51-6.
116. Bertolotto C, Lesueur F, Giuliano S, et al. A SUMOylationdefective MITF germline mutation predisposes to melanoma and renal carcinoma. Nature 2011; 480: 94-8.
117. Curtin JA, Fridlyand J, Bastian BC, et al. Distinct sets of genetic alterations in melanoma. N Engl J Med 2005; 353: 2135-47.
118. Gajewski TF. Molecular profiling of melanoma and the evolution of patient-specific therapy. Semin Oncol 2011; 38: 236-42.
119. Vidwans SJ, Flaherty KT, Fisher DE, Tenenbaum JM, Travers MD, Shrager J. A melanoma molecular disease model. PLoS One 2011; 6: e18257
120. Sekulic A, Haluska P Jr, Miller AJ, et al; Melanoma Study Group of Mayo Clinic Cancer Center. Malignant melanoma in the 21st century: the emerging molecular landscape. Mayo Clin Proc 2008; 83: 825-46.
121. Postow MA, Carvajal RD. Therapeutic implications of KIT in melanoma. Cancer J 2012; 18: 137-41.
122. Dumaz N. Mechanism of RAF isoform switching induced by oncogenic RAS in melanoma. Small Gtpases 2011; 2: 289-92.
123. Flaherty KT, Hodi FS, Fisher DE. From genes to drugs: targeted strategies for melanoma. Nature Rev Cancer 2012; 12: 349-61.
124. Padua RA, Barrass N, Currie GA. A novel transforming gene in a human malignant melanoma cell line. Nature 1984; 311: 671-3.
125. Fecher LA, Cummings SD, Keefe MJ, Alani RM. Toward a molecular classification of melanoma. J Clin Oncol 2007; 25: 1606-20.
126. Kormos B, Belso N, Bebes A, et al. In vitro dedifferentiation of melanocytes from adult epidermis. PLoS One 2011; 6: e17197.
127. Grichnik JM. Melanoma, Nevogenesis, and Stem Cell Biology. J Invest Dermatol 2008; 128: 2365-80.
128. White RM, Zon LI. Melanocytes in development, regeneration, and cancer. Cell Stem Cell 2008; 3: 242-52.
129. Bondanza S, Bellini M, Roversi G, et al. Piebald trait: implication of kit mutation on in vitro melanocyte survival and on the clinical application of cultured epidermal autografts. J Invest Dermatol 2007; 127: 676-86.
130. Hou L, Panthier JJ, Arnheiter H. Signaling and transcriptional regulation in the neural crest-derived melanocyte lineage: interactions between KIT and MITF. Development 2000; 127: 5379-89.
131. Aoki H, Hara A, Motohashi T, Kunisada T. Protective effect of Kit signaling for melanocyte stem cells against radiation-induced genotoxic stress. J Invest Dermatol 2011; 131: 1906-15.
132. Easty DJ, Gray SG, O'Byrne KJ, O'Donnell D, Bennett DC. Receptor tyrosine kinases and their activation in melanoma. Pigment Cell Melanoma Res 2011; 24: 446-61.
133. Alexeev V, Yoon K. Distinctive role of the cKit receptor tyrosine kinase signaling in mammalian melanocytes. J Invest Dermatol 2006; 126: 1102-10.
134. Carvajal RD, Antonescu CR, Wolchok JD, et al. KIT as a therapeutic target in metastatic melanoma. JAMA 2011; 305: 2327-34.
135. Janku F, Novotny J, Julis I, et al. KIT receptor is expressed in more than 50% of early-stage malignant melanoma: a retrospective study of 261 patients. Melanoma Res 2005; 15: 251-6.
136. Schoenewolf NL, Bull C, Belloni B, et al. Sinonasal, genital and acrolentiginous melanomas show distinct characteristics of KIT expression and mutations. Eur J Cancer 2012; 48: 1842-52.
137. Schoenewolf NL, Urosevic-Maiwald M, Dummer R. Tumor heterogeneity of mucosal melanomas during treatment with Imatinib. Br J Dermatology 2011; 165: 419-24.
138. Eggermont AM, Robert C. Melanoma in 2011: a new paradigm tumor for drug development. Nat Rev Clin Oncol 2012; 9: 74-6.
139. Whiteman DC, Pavan WJ, Bastian BC. The melanomas: A synthesis of epidemiological, clinical, histopathological, genetic, and biological aspects, supporting distinct subtypes, causal pathways, and cells of origin. Pigment Cell Melanoma Res 2011; 24: 879-97.
140. Beadling C, Jacobson-Dunlop E, Hodi FS, et al. KIT gene mutations and copy number in melanoma subtypes. Clin Cancer Res 2008; 14: 6821-8.
141. Curtin JA, Busam K, Pinkel D, Bastian BC. Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol 2006; 24: 4340-6.
142. Willmore-Payne C, Holden JA, Tripp S, et al. Human malignant melanoma: Detection of BRAF-and c-kit-ctivating mutations by high-resolution amplicon melting analysis. Hum Pathol 2005; 36: 486-93.
143. Halaban R, Zhang W, Bacchiocchi A, et al. PLX4032, a selective BRAF(V600E) kinase inhibitor, activates the ERK pathway and enhances cell migration and proliferation of BRAF melanoma cells. Pigment Cell Melanoma Res 2010; 23: 190-200.
144. Sharma SV, Settleman J. Oncogene addiction: setting the stage for molecularly targeted cancer therapy. Genes Dev 2007; 21: 3214-31.
145. Weinstein IB, Joe A. Oncogene addiction. Cancer Res 2008; 68: 3077-80.
146. Dhomen N, Marais R. BRAF signaling and targeted therapies in melanoma. Hematol. Oncol. Clin. North Am 2009; 23: 529-45.
147. Smalley KS, Nathanson KL, Flaherty KT. Genetic subgrouping of melanoma reveals new opportunities for targeted therapy. Cancer Res 2009; 69: 3241-4.
148. Flaherty KT, Yasothan U, Kirkpatrick P. Vemurafenib. Nat Rev Drug Discov 2011; 10: 811-2.
149. Amaria RN, Lewis KD, Jimeno A. Vemurafenib: the road to personalized medicine in melanoma. Drugs Today 2012; 48: 109-18.
150. Vidwans SJ, Flaherty KT, Fisher DE, Tenenbaum JM, Travers MD, Shrager J. A melanoma molecular disease model. PLoS One 2011; 6: e18257.
151. Lutzky J, Bauer J, Bastian BC. Dose-dependent, complete response to imatinib of a metastatic mucosal melanoma with a K642E KIT mutation. Pigment Cell Melanoma Res 2008; 21: 492-3.
152. Quintás-Cardama A, Lazar AJ, Woodman SE, Kim K, Ross M, Hwu P. Complete response of stage IV anal mucosal melanoma expressing KIT Val560Asp to the multikinase inhibitor sorafenib. Nat Clin Pract Oncol 2008; 5: 737-40.
153. Dummer R, Hauschild A, Guggenheim M, Melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010; 21: v194-7
154. Mangana J, Levesque MP, Karpova MB, Dummer R. Sorafenib in melanoma. Expert Opin Investig Drugs 2012; 21: 557-68.
155. Stirewalt DL, Meshinchi S. Receptor tyrosine kinase alterations in AML-biology and therapy. Cancer Treat Res 2010; 145: 85-108.
156. Haferlach T. Molecular genetic pathways as therapeutic targets in acute myeloid leukemia. Hematology Am Soc Hematol Educ Program 2008; 400-11.
157. Pawson T. Regulation and targets of receptor tyrosine kinases. Eur J Cancer 2002; 38: S3-10.
158. Arora A, Scholar P. Role of tyrosine kinase inhibitors in cancer therapy. J Pharmacol Exp Ther 2005; 315: 971-9.
159. Reilly J. Pathogenesis of acute myeloid leukaemia and inv(16)(p13;q22):a paradigm for understanding leukaemogenesis? Br J Haematol 2005; 128: 18-34.
160. Marcucci G, Haferlach T, Döhner H. Molecular genetics of adult acute myeloid leukemia: prognostic and therapeutic implications. J Clin Oncol 2011; 29: 475-86.
161. Döhner K, Döhner H: Molecular characterization of acute myeloid leukemia. Haematologica 2008; 93: 976-82.
162. Fos J, Pabst T, Petkovic V, Ratschiller D, Mueller BU. Deficient CEBPA DNA binding function in normal karyotype AML patients is associated with favorable prognosis. Blood 2011; 117: 4881-4.
163. Motyckova G, Stone RM. The role of molecular tests in acute myelogenous leukemia treatment decisions. Curr Hematol Malig Rep 2010; 5: 109-17.
164. Odenike O, Thirman MJ, Artz AS, Godley LA, Larson RA, Stock W. Gene Mutations, Epigenetic Dysregulation, and Personalized Therapy in Myeloid Neoplasia: Are We There Yet? Semin Oncol 2011; 38: 196-214.
165. Wang YY, Zhao LJ, Wu CF, et al. C-KIT mutation cooperates with full-length AML1-ETO to induce acute myeloid leukemia in mice. Proc Natl Acad Sci USA 2011; 108: 2450-5.
166. Shen Y, Zhu YM, Fan X, et al. Gene mutation patterns and their prognostic impact in a cohort of 1185 patients with acute myeloid leukemia. Blood 2011; 118: 5593-603.
167. Thiede C. Mutant DNMT3A: teaming up to transform. Blood 2012; 119: 5615-7.
168. Ribeiro AFT, Pratcorona M, Erpelinck-Verschueren C, et al. Mutant DNMT3A: a marker of poor prognosis in acute myeloid leukemia. Blood 2012; 119: 5824-31.
169. Hassan HT. c-Kit expression in human normal and malignant stem cells prognostic and therapeutic implications. Leuk Res 2009; 33: 5-10.
170. Miettinen M, Lasota J. KIT (CD117): A review on expression in normal and neoplastic tissues, and mutations and their clinicopathologic correlation. Appl Immunohistochem Mol Morphol 2005; 13: 205-20.
171. Malaise M, Steinbach D, Corbacioglu S. Clinical implications of c-Kit mutations in acute myelogenous leukemia. Current Hematologic Malignancy Reports, 2009; 4: 77-82.
172. Cáceres-Cortés JR. Blastic leukaemias (AML): A biologist's view. Cell Biochem Biophys 2012; doi: 10.1007/s12013-012-9392-8.
173. Vercauteren SM, Sutherland HJ. CD133 (AC133) expression on AML cells and progenitors. Cytotherapy 2001; 3: 449-59
174. Scolnik MP, Morilla R, de Bracco MM, et al. CD34 and CD117 are overexpressed in AML and may be valuable to detect minimal residual disease. Leuk Res 2002; 26: 615-9
175. Kawakita M, Yonemura Y, Miyake H, et al. Soluble c-kit molecule in serum from healthy individuals and patients with haematopoietic disorders. Br J Haematol 1995; 91: 23-9
176. Bono P, Krause A, von Mehren M, et al. Serum KIT and KIT ligand levels in patients with gastrointestinal stromal tumors treated with imatinib. Blood 2004; 103: 2929-35.
177. Bains A, Lu G, Yao H, et al. Molecular and clinicopathologic characterization of AML with isolated trisomy 4. Am J Clin Pathol 2012; 137: 387-94.
178. Del Poeta G, Venditti A, Del Principe MI, et al. Amount of spontaneous apoptosis detected by bax/bcl-2 ratio predicts outcome in acute myeloid leukemia (AML). Blood 2003; 101: 2125-31.
179. Gao XN, Lin J, Li YH, et al. MicroRNA-193a represses c-kit expression and functions as a methylation-silenced tumor suppressor in acute myeloid leukemia. Oncogene 2011; 30: 3416-28.
180. Paschka P, Marcucci G, Ruppert AS, et al; Cancer and Leukemia Group B. Adverse prognostic significance of KIT mutations in adult acute myeloid leukemia with inv(16) and t(8;21): a Cancer and Leukemia Group B Study. J Clin Oncol 2006; 24: 3904-11.
181. 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: 1104-9.
182. Schessl C, Rawat VPS, 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: 2159-68.
183. 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: 1806-9.
184. Doepfner KT, Boller D, Arcaro A. Targeting receptor tyrosine kinase signaling in acute myeloid leukemia. Crit Rev Oncol Hematol 2007; 63: 215-30.
185. Speck NA, Gilliland DG. Core-binding factors in haematopoiesis and leukaemia. Nat Rev Cancer 2002; 2: 502-13.
186. Boissel N, Leroy H, Brethon B, et al. Incidence and prognostic impact of c-kit, FLT3, and Ras gene mutations in core binding factor acute myeloid leukemia (CBF-AML). Leukemia 2006; 20: 965-70.
187. Care RS, Valk PJM, Goodeve AC, et al. Incidence and prognostic of c-KIT and FLT3 mutations in core binding factor (CBF) acute myeloid leukaemias. Br J Haematol 2003; 121: 775-7.
188. 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: 3958-61.
189. Kindler T, Breitenbuecher F, Marx A, et al. Efficacy and safety of imatinib in adult patients with c-kit-positive acute myeloid leukemia. Blood 2004; 103: 3644-54.
190. Park SH, Chi HS, Min SK, et al. Prognostic impact of c-kit mutations in core binding factor acute myeloid leukemia Leukemia Res 2011; 35: 1376-83
191. Dohner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European Leukemia Net. Blood 2010; 115: 453-74.
192. Laine E, Chauvot de Beauchene I, Perahia D, Auclair C, Tchertanov L. Mutation D816V alters the internal structure and dynamics of c-KIT receptor cytoplasmic region: implications for dimerization and activation mechanisms. PLoS Comput Biol 2011; 7: e1002068.
193. Renneville A, Roumier C, Biggio V, et al. Cooperating gene mutations in acute myeloid leukemia: a review of the literature. Leukemia 2008; 22: 915-31.
194. Stankov K, Stankov S, Popovic S. Translational research in complex etiopathogenesis and therapy of hematological malignancies: the specific role of tyrosine kinases signaling and inhibition. Med Oncol 2009; 26: 437-44.
195. Patnaik MM, Tefferi A, Pardanani A. Kit: molecule of interest for the diagnosis and treatment of mastocytosis and other neoplastic disorders. Curr Cancer Drug Targets 2007; 7: 492-503.
196. Kindler T, Breitenbuecher F, Marx A, et al. Sustained complete hematologic remission after administration of the tyrosine kinase inhibitor imatinib mesylate in a patient with refractory, secondary AML. Blood 2003; 101: 2960-2.
197. Estey EH. How to manage high-risk acute myeloid leukemia. Leukemia 2012; 26: 861-9.
198. Correll PH, Paulson RF, Wei X. Molecular regulation of receptor tyrosine kinases in hematopoietic malignancies. Gene 2006; 374: 26-38
199. De J, Zanjani R, Hibbard M, Davis BD. Immunophenotypic profile predictive of KIT activating mutations in AML1-ETO leukemia. Am J Clin Pathol 2007; 128: 550-7
200. Ohanian M, Cortes J, Kantarjian H, Jabbour E. Tyrosine kinase inhibitors in acute and chronic leukemias. Expert Opin Pharmacother 2012; 13: 927-38.
201. Hu S, Niu H, Minkin P, et al. Comparison of antitumor effects of multitargeted tyrosine kinase inhibitors in acute myelogenous leukemia. Mol Cancer Ther 2008; 7: 1110-20.
202. Krug U, Lübbert M, Büchner T. Maintenance therapy in acute myeloid leukemia revisited: will new agents rekindle an old interest? Curr Opin Hematol 2010; 17: 85-90.
203. Advani AS, Tiu R, Saunthararajah Y, et al. A Phase 1 study of imatinib mesylate in combination with cytarabine and daunorubicin for c-kit positive relapsed acute myeloid leukemia. Leuk Res 2010; 34: 1622-6.
204. Brandwein JM, Hedley DW, Chow S, et al. A phase I/II study of imatinib plus reinduction therapy for c-kit-positive relapsed/ refractory acute myeloid leukemia: inhibition of Akt activation correlates with complete response. Leukemia 2011; 25: 945-52.
205. Dibb NJ, Dilworth SM, Mol CD. Switching on kinases: oncogenic activation of BRAF and the PDGFR family. Nat Rev Cancer 2004; 4: 718-27.
206. Fernández A, Sanguino A, Peng Z, et al. Rational drug redesign to overcome drug resistance in cancer therapy: imatinib moving target. Cancer Res 2007; 67: 4028-33.
207. Azam M, Nardi V, Shakespeare WC, et al. Activity of dual SRCABL inhibitors highlights the role of BCR/ABL kinase dynamics in drug resistance. Proc Natl Acad Sci USA 2006; 103: 9244-9.
208. Widmer N, Decosterd LA, Leyvraz S, et al. Relationship of imatinib-free plasma levels and target phenotype with efficacy and tolerability. Br J Cancer 2008; 98: 1633-40.
209. Wang L, Giannoudis A, Lane S, et al. Expression of the uptake drug transporter hOCT1 is an important clinical determinant of the response to imatinib in chronic myeloid leukemia. Clin Pharmacol Ther 2008;83:258-64.
210. Paun O, Lazarus HM. Allogeneic hematopoietic cell transplantation for acute myeloid leukemia in first complete remission: have the indications changed? Curr Opin Hematol 2012;19:95-101.
211. Dubreuil P, Letard S, Ciufolini M, et al. Masitinib (AB1010), a potent and selective tyrosine kinase inhibitor targeting KIT. PLoS One 2009; 4: e7258.
212. Wilhelm SM, Dumas J, Adnane L, et al. Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int J Cancer 2011; 129: 245-55.
213. Eskens FA, Steeghs N, Verweij J, et al. Phase I dose escalation study of telatinib, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor 2 and 3, platelet-derived growth factor receptor beta, and c-Kit, in patients with advanced or metastatic solid tumors. Journal of Clinical Oncology, 2009; 27: 4169-76.
214. Fang HT, Zhang B, Pan XF, et al. Bortezomib interferes with CKIT processing and transforms the t(8;21)-generated fusion proteins into tumor-suppressing fragments in leukemia cells. Proc Natl Acad Sci USA 2012; 109: 2521-6.
215. Levitzki A, Mishani E. Tyrphostins and other tyrosine kinase inhibitors. Ann Rev Biochem 2006; 75: 93-109.
216. Caceres-Cortes JR. A potent anti-carcinoma and anti acute myeloblastic leukemia agent, AG490. Anticancer Agents in Medicinal Chemistry, 2008; 8: 717-22.
217. Quintas-Cardama A, Cortes J. Nilotinib: a phenylamino-pyrimidine derivative with activity against BCR-ABL, KIT and PDGFR kinases. Future Oncol 2008; 4: 611-21.
218. Shah NP, Lee FY, Luo R, Jiang Y, Donker M, Akin C. Dasatinib (BMS-354825) inhibits KITD816V, an imatinib-resistant activating mutation that triggers neoplastic growth in most patients with systemic mastocytosis. Blood 2006; 108: 286-91.
219. 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: 473-81.
220. Smith CC, Wang Q, Chin CS, et al. Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia. Nature 2012; 485: 260-3.
221. Zarrinkar PP, Gunawardane RN, Cramer MD, et al. AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML). Blood 2009; 114: 2984-92.
222. Rosen DB, Cordeiro JA, Cohen A, et al. Assessing signaling pathways associated with in vitro resistance to cytotoxic agents in AML. Leuk Res 2012; 36: 900-4.
223. Levis M, Allebach J, Tse KF, et al. A FLT3-targeted tyrosine kinase inhibitor is cytotoxic to leukaemia cells in vitro and in vivo. Blood 2002; 99:3885-91
224. Buccisano F, Maurillo L, Del Principe MI, et al. Prognostic and therapeutic implications of minimal residual disease detection in acute myeloid leukemia. Blood 2012; 119: 332-41.
225. Ommen HB, Schnittger S, Jovanovic JV, et al. Strikingly different molecular relapse kinetics in NPM1c, PML-RARA, RUNX1-RUNX1T1, and CBFB-MYH11 acute myeloid leukemias. Blood 2010; 115: 198-205.
226. Levi F, Lucchini F, Negri E, Barbui T, La Vecchia C. Trends in mortality from leukemia in subsequent age groups. Leukemia 2000; 14: 1980-5.
227. Sattler M, Salgia R. Targeting c-Kit mutations: basic science to novel therapies. Leuk Res 2004; 28: S11-20.
228. Georgin-Lavialle S, Lhermitte L, Suarez F, et al. Mast cell leukemia: identification of a new c-Kit mutation, dup(501-502), and response to masitinib, a c-Kit tyrosine kinase inhibitor. Eur J Hematol 2012; 89: 47-52.
229. Mital A, Piskorz A, Lewandowski K, Wasag B, Limon J, Hellmann A. A case of mast cell leukemia with exon 9 mutation and good response to imatinib. Eur J Hematol 2011; 86: 531-5.
230. Orfao A, Garcia-Montero AC, Sanchez L, Escribano L; REMA. Recent advances in the understanding of mastocytosis: the role of KIT mutations. Br J Haem 2007; 138: 12-30.
231. Sattler M, Salgia R. Targeting c-Kit mutations: basic science to novel therapies. Leuk Res 2004; 28: S11-20.
232. Ma Y, Zeng S, Metcalfe DD, et al. The c-KIT mutation causing human mastocytosis is resistant to STI571 and other KIT kinase inhibitors kinases with enzymatic site mutations show different inhibitor sensitivity profiles than wildtype kinases and those with regulatory-type mutations. Blood 2002; 99: 1741-4.
233. Sattler M, Salgia R. Targeting c-Kit mutations: basic science to novel therapies. Leuk Res 2004; 28: S11-20.
234. Kristensen T, Broesby-Olsen S, Vestergaard H, et al. Circulating KIT D816V mutation-positive non-mast cells in peripheral blood are characteristic of indolent systemic mastocytosis. Eur J Haematol 2012; 89: 42-6.
235. Pardanani A, Akin C, Valent P. Pathogenesis, clinical features, and treatment advances in mastocytosis. Best Pract Res Clin Haematol 2006;19: 595-615.
236. Daley T, Metcalfe DD, Akin C. Association of the Q576R polymorphism in the interleukin-4 receptor % chain with indolent mastocytosis limited to the skin. Blood 2001; 98: 880-2.
237. Metcalfe DD. Mast cells and mastocytosis. Blood 2008; 112: 946-56.
238. Corbin AS, Demehri S, Griswold IJ et al. In vitro and in vivo activity of ATP-based kinase inhibitors AP23464 and AP23848 against activation loop mutants of Kit. Blood 2005; 106: 227-34.
239. Tanaka A, Konno M, Muto S et al. A novel NF-{kappa}B inhibitor, IMD-0354, suppresses neoplastic proliferation of human mast cells with constitutively activated c-kit receptors. Blood 2005; 105: 2324-31.
240. Yee SB, Kim MS, Baek SJ et al. Trichostatin A induces apoptosis of p815 mastocytoma cells in histone acetylation-and mitochondria-dependent fashion. Int J Oncol 2004; 25: 1431-6.
241. Valent P, Cerny-Reiterer S, Herrmann H, et al. Phenotypic heterogeneity, novel diagnostic markers, and target expression profiles in normal and neoplastic human mast cells. Best Pract Res Clin Haematol 2010; 23: 369-78.
242. Gleixner KV, Mayerhofer M, Sonneck K, et al. Synergistic growthinhibitory effects of two tyrosine kinase inhibitors, dasatinib and PKC412, on neoplastic mast cells expressing the D816V-mutated oncogenic variant of KIT. Haematologica 2007; 92: 1451-9.
243. Ustun C, DeRemer D, Akim C. Tyrosine kinase inhibitors in the treatment of systemic mastocytosis. Leuk Res 2011; 35: 1143-52.