Therapeutic efficacy of prenylation inhibitors in the treatment of myeloid leukemia

Leukemia

Volumn 17, Issue 8, 2003, Pages 1482-1498

  Morgan, M A ^a   Ganser, A ^a   Reuter, C W M ^a  

^a HANNOVER MEDICAL SCHOOL   (Germany)

Author keywords

Farnesylation; FTI; Geranylgeranylation; Myeloid leukemia; Prenylation; RAS

Indexed keywords

3 BENZYL 7 CYANO 2,3,4,5 TETRAHYDRO 1 (1H IMIDAZOL 4 YLMETHYL) 4 (2 THIENYLSULFONYL) 1H 1,4 BENZODIAZEPINE; ANTINEOPLASTIC AGENT; CAPECITABINE; CYTARABINE; DOCETAXEL; FARNESYL TRANS TRANSFERASE; FLUOROURACIL; FOLINIC ACID; GEMCITABINE; GGTI 2133; GGTI 2147; GGTI 286; GGTI 287; GGTI 297; GGTI 298; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; IRINOTECAN; L 778123; LONAFARNIB; MEVINOLIN; PROTEIN FARNESYLTRANSFERASE INHIBITOR; RAS PROTEIN; RETINOIC ACID; SIMVASTATIN; TIPIFARNIB; TOPOTECAN; TRASTUZUMAB; UNCLASSIFIED DRUG;

ACUTE GRANULOCYTIC LEUKEMIA; ANEMIA; ANGIOGENESIS; ANOREXIA; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; AREA UNDER THE CURVE; ATAXIA; BODY WEIGHT DISORDER; BONE MARROW SUPPRESSION; BRADYCARDIA; CANCER GROWTH; CELL DIFFERENTIATION; CELL GROWTH; CELL MEMBRANE; CHRONIC MYELOID LEUKEMIA; CLINICAL TRIAL; CONFUSION; DIARRHEA; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DESIGN; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENTIATION; DRUG RESISTANCE; DRUG TARGETING; DYSARTHRIA; FATIGUE; HEADACHE; HEART ARRHYTHMIA; HEART ATRIUM FIBRILLATION; HUMAN; HYPERBILIRUBINEMIA; HYPOKALEMIA; HYPOTENSION; INFECTION; KIDNEY FAILURE; LIVER DYSFUNCTION; LIVER TOXICITY; LONG QT SYNDROME; MAXIMUM TOLERATED DOSE; MONOTHERAPY; MYELODYSPLASTIC SYNDROME; MYELOID LEUKEMIA; NAUSEA; NEUROPATHY; NEUROTOXICITY; NEUTROPENIA; ONCOGENE; PARESTHESIA; PATHOGENESIS; POLYDIPSIA; PRENYLATION; PRIORITY JOURNAL; PROTEIN LOCALIZATION; PROTEIN MODIFICATION; PROTEIN PROCESSING; PROTEIN TARGETING; RASH; REVIEW; SIGNAL TRANSDUCTION; SOMNOLENCE; SUPRAVENTRICULAR TACHYCARDIA; THROMBOCYTOPENIA; VOMITING; WEIGHT REDUCTION;

EID: 0041526704     PISSN: 08876924     EISSN: None     Source Type: Journal    
DOI: 10.1038/sj.leu.2403024     Document Type: Review

References (216)

1. Reuter CWM, Morgan MA, Bergmann L. Targeting the Ras signaling pathway: a rational, mechanism-based treatment for hematological malignancies? Blood 2000; 96: 1655-1669.
2. Hahn SM, Bernhard E, McKenna WG. Farnesyltransferase inhibitors. Semin Oncol 2001; 28: 86-93.
3. Rosenblatt JD, Rowe JM. Introduction. Semin Hematol 2002; 39: 1-3.
4. Reuther GW, Der CJ. The Ras branch of small GTPases: Ras family members don't fall far from the tree. Curr Opin Cell Biol 2000; 12: 157-165.
5. Rebollo A, Martinez CA. Ras proteins: recent advances and new functions. Blood 1999; 94: 2971-2980.
6. Mumby SM. Reversible palmitoylation of signaling proteins. Curr Opin Cell Biol 1997; 9: 148-154.
7. Wittinghofer A. Signal transduction via Ras. Biol Chem 1998; 379: 933-937.
8. Marshall CJ. Ras effectors. Curr Opin Cell Biol 1996; 8: 197-204.
9. Katz ME, McCormick F. Signal transduction from multiple Ras effectors. Curr Opin Genet Dev 1997; 7: 75-79.
10. Feig LA, Urano T, Cantor S. Evidence for a Ras/Ral signaling cascade. Trends Biochem Sci 1996; 21: 438-441.
11. Carpenter CL, Cantley LC. Phosphoinositide kinases. Curr Opin Cell Biol 1996; 8: 153-158.
12. Lee Jr JT, McCubrey JA. The Raf/MEK/ERK signal transduction cascade as a target for chemotherapeutic intervention in leukemia. Leukemia 2002; 16: 486-507.
13. McCubrey JA, Steelman LS, Hoyle PE, Blalock WL, Weinstein-Oppenheimer C, Franklin RA et al. Differential abilities of activated Raf oncoproteins to abrogate cytokine dependency, prevent apoptosis and induce autocrine growth factor synthesis in human hematopoietic cells. Leukemia 1998; 12: 1903-1929.
14. Blalock WL, Weinstein-Oppenheimer C, Chang F, Hoyle PE, Wang XY, Algate PA et al. Signal transduction, cell cycle regulatory, and anti-apoptotic pathways regulated by IL-3 in hematopoietic cells: possible sites for intervention with antineoplastic drugs. Leukemia 1999; 13: 1109-1166.
15. Blalock WL, Moye PW, Chang F, Pearce M, Steelman LS, McMahon M et al. Combined effects of aberrant MEK1 activity and BCL2 overexpression on relieving the cytokine dependency of human and murine hematopoietic cells. Leukemia 2000; 14: 1080-1096.
16. Blalock WL, Pearce M, Steelman LS, Franklin RA, McCarthy SA, Cherwinski H et al. A conditionally-active form of MEK1 results in autocrine transformation of human and mouse hematopoietic cells. Oncogene 2000; 19: 526-536.
17. Hoyle PE, Moye PW, Steelman LS, Blalock WL, Franklin RA, Pearce M et al. Differential abilities of the Raf family of protein kinases to abrogate cytokine dependency and prevent apoptosis in murine hematopoietic cells by a MEK1-dependent mechanism. Leukemia 2000; 14: 642-656.
18. Moye PW, Blalock WL, Hoyle PE, Chang F, Franklin RA, Weinstein-Oppenheimer C et al. Synergy between Raf and BCL2 in abrogating the cytokine dependency of hematopoietic cells. Leukemia 2000; 14: 1060-1079.
19. Weinstein-Oppenheimer C, Steelman LS, Algate PA, Blalock WL, Burrows C, Hoyle PE et al. Effects of deregulated Raf activation on integrin, cytokine-receptor expression and the induction of apoptosis in hematopoietic cells. Leukemia 2000; 14: 1921-1938.
20. Blalock WL, Pearce M, Chang F, Lee JT, Pohnert SC, Burrows C et al. Effects of inducible MEK1 activation on the cytokine dependency of lymphoid cells. Leukemia 2001; 15: 794-807.
21. White MK, McCubrey JA. Suppression of apoptosis: role in cell growth and neoplasia. Leukemia 2001; 15: 1011-1021.
22. Bos JL. RAS oncogenes in human cancer: a review. Cancer Res 1989; 49: 4682-4689.
23. Clark GJ, Der CJ. Ras proto-oncogene activation in human malignancy. In: Garrett CT, Sell S (eds), Cellular Cancer Markers. Totowa, New Jersey: Humana Press, 1995, pp 17-52.
24. Scheffzek K, Ahmadian MR, Kabsch W, Wiesmuller L, Lautwein A, Schmitz F et al. The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants. Science 1997; 277: 333-338.
25. Lin SR, Tsai JH, Yang YC, Lee SC. Mutations of K-Ras oncogene in human adrenal tumors in Taiwan. Br J Cancer 1998; 77: 1060-1065.
26. Lin SR, Hsu CH, Tsai JH, Wang JY, Hsieh TJ, Wu CH. Decreased GTPase activity of K-Ras deriving from human functional adrenocortical tumours. Br J Cancer 2000; 82. 1035-1040.
27. Sprang SR. G protein mechanisms: insights from structural analysis. Ann Rev Biochem 1997; 66: 639-678.
28. Byrne JL, Marshall CJ. The molecular pathophysiology of myeloid leukaemias: Ras revisited. Br J Haematol 1998; 100: 256-264.
29. Sawyers CL, Denny CT. Chronic myelomonocytic leukemia: Tel-a-kinase what its all about. Cell 1994; 77: 171-173.
30. Beaupre DM, Kurzrock R. RAS and leukemia: from basic mechanisms to gene-directed therapy. J Clin Oncol 1999; 17: 1071-1079.
31. 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.
32. Kitayama H, Kanakura Y, Furitsu T, Tsujimura T, Oritani K, Ikeda H et al. Constitutively activating mutations of c-Kit receptor tyrosine kinase confer factor-independent growth and tumorigenicity of factor-dependent hematopoietic cell lines. Blood 1995; 85: 790-798.
33. Nakata Y, Kimura A, Katoh O, Kawaishi K, Hyodo H, Abe K et al. c-Kit point mutation of extracellular domain in patients with myeloproliferative disorders. Br J Haematol 1995; 91: 661-663.
34. Dosil M, Wang S, Lemischka IR. Mitogenic signaling and substrate specificity of the Flk2/Flt3 receptor tyrosine kinase in fibroblasts and interleukin 3-dependent hematopoietic cells. Mol Cell Biol 1993; 13: 6572-6585.
35. Kiyoi H, Naoe T, Nakano Y, Yokota S, Minami S, Miyawaki S et al. Prognostic implication of FLT3 and N-Ras gene mutations in acute myeloid leukemia. Blood 1999; 93: 3074-3080.
36. Golub T, Barker G, Lovett M, Gilliland D. Fusion of PDGF receptor β to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation. Cell 1994; 77: 307-316.
37. Jousset C, Carron C, Boureux A, Quang CT, Oury C, Dusanter-Fourt I et al. Adomain of TEL conserved in a subset of ETS proteins defines a specific oligomerization interface essential to the mitogenic properties of the TEL-PDGFRβ oncoprotein. EMBO J 1997; 16: 69-82.
38. Papadopoulos P, Raidge SA, Boucher CA, Stocking C, Wiedemann LM. The novel activation of abl by fusion to an ets-related gene, tel. Cancer Res 1995; 55: 34-38.
39. Golub TR, Goga A, Barker GF, Afar DE, McLaughlin J, Bohlander SK et al. Oligomerization of the ABL tyrosine kinase by the Ets protein TEL in human leukemia. Mol Cell Biol 1996; 16: 4107-4116.
40. Zou X, Calame K. Signaling pathways activated by oncogenic forms of Abl tyrosine kinase. J Biol Chem 1999; 274: 18141-18144.
41. Voss J, Posern G, Hannemann JR, Wiedemann LM, Turhan AG, Poirel H et al. The leukaemic oncoproteins BCR-Abl and Tel-Abl (ETV6/Abl) have altered substrate preferences and activate similar intracellular signaling pathways. Oncogene 2000; 19: 1684-1690.
42. DeClue JE, Papageorge AG, Fletcher JA, Diehl SR, Ratner N, Vass WC et al. Abnormal regulation of mammalian p21 ras contributes to malignant tumor growth in von Recklinghausen (type 1) neurofibromatosis. Cell 1992; 69: 265-273.
43. Kalra R, Paderanga DC, Olson K, Shannon KM. Genetic analysis is consistent with the hypothesis that NF-1 limits myeloid cell growth through p21 ras. Blood 1994; 84: 3435-3439.
44. Bollag G, Clapp DW, Shih S, Adler F, Zhang YY, Thompson P et al. Loss of NF1 results in activation of the Ras signaling pathway and leads to aberrant growth in haematopoietic cells. Nat Genet 1996; 12: 144-148.
45. Largaespada DA, Brannan CI, Jenkins NA, Copeland NG. NF-1 deficiency causes Ras-mediated granulocyte/macrophage colony stimulating factor hypersensitivity and chronic myeloid leukemia. Nat Genet 1996; 12: 137-143.
46. Largaespada DA. Genetic heterogeneity in acute myeloid leukemia: maximizing information flow from MuLV mutagenesis studies. Leukemia 2000; 14: 1174-1184.
47. Horiike S, Yokota S, Nakao M, Iwai T, Sasai Y, Kaneko H et al. Tandem duplications of the FLT3 receptor gene are associated with leukemic transformation of myelodysplasia. Leukemia 1997; 11: 1442-1446.
48. Yokota S, Kiyoi H, Nakao M, Iwai T, Misawa S, Okuda T 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.
49. Kiyoi H, Towatari M, Yokota S, Hamaguchi M, Ohno R, Saito H 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.
50. Rombouts WJ, Blokland I, Lowenberg B, Ploemacher RE. Biological characteristics and prognosis of adult acute myeloid leukemia with internal tandem duplications in the Flt3 gene. Leukemia 2000; 14: 675-683.
51. Noguera NI, Breccia M, Divona M, Diverio D, Costa V, De Santis S et al. Alterations of the FLT3 gene in acute promyelocytic leukemia: association with diagnostic characteristics and analysis of clinical outcome in patients treated with the Italian AIDA protocol. Leukemia 2002; 16: 2185-2189.
52. Iwai T, Yokota S, Nakao M, Okamoto T, Taniwaki M, Onodera N et al. Internal tandem duplication of the FLT3 gene and clinical evaluation in childhood acute myeloid leukemia. The Children's Cancer and Leukemia Study Group, Japan. Leukemia 1999; 13: 38-43.
53. Xu F, Taki T, Eguchi M, Kamada N, Ishii E, Endo M et al. Tandem duplication of the FLT3 gene is infrequent in infant acute leukemia. Japan Infant Leukemia Study Group. Leukemia 2000; 14: 945-957.
54. Rubnitz JE, Raimondi SC, Halbert AR, Tong X, Srivastava DK, Razzouk BI et al. Characteristics and outcome of t(8;21)-positive childhood acute myeloid leukemia: a single institution's experience. Leukemia 2002; 16: 2072-2077.
55. Zhao M, Kiyoi H, Yamamoto Y, Ito M, Towatari M, Omura S et al. In vivo treatment of mutant FLT3-transformed murine leukemia with a tyrosine kinase inhibitor. Leukemia 2000; 14: 348-374.
56. 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.
57. Minami Y, Kiyoi H, Yamamoto Y, Yamamoto K, Ueda R, Saito H et al. Selective apoptosis of tandemly duplicated FLT3-transformed leukemia cells by Hsp90 inhibitors. Leukemia 2002; 16: 1535-1540.
58. Rohrschneider LR, Bourette RP, Lioubin MN, Algate PA, Myles GM, Carlberg K. Growth and differentiation signals regulated by the M-CSF receptor. Mol Reprod Dev 1997; 46: 96-103.
59. Hunter T. Oncoprotein networks. Cell 1997; 88: 333-346.
60. Kurzrock R, Gutterman JU, Talpaz M. The molecular genetics of Philadelphia chromosome-positive leukemias. N Engl J Med 1988; 319: 990-998.
61. Faderl S, Talpaz M, Estrov Z, O'Brien S, Kurzrock R, Kantarjian HM. The biology of chronic myeloid leukemia. N Engl J Med 1999; 341: 164-172.
62. Miyauchi J, Asada M, Sasaki M, Tsunematsu Y, Kojima S, Mizutani S. Mutations of the N-ras gene in juvenile chronic myelogenous leukemia. Blood 1994; 83: 2248-2254.
63. Birnbaum RA, O'Marcaigh A, Wardak Z, Zhang YY, Dranoff G, Jacks T et al. Nf1 and Gmcsf interact in myeloid leukemogenesis. Mol Cell 2000; 5: 189-195.
64. Hotte SJ, Hirte HW. BAY 43-9006: early clinical data in patients with advanced solid malignancies. Curr Pharm Des 2002; 8: 2249-2253.
65. Sebti SM, Hamilton AD. Farnesyltransferase and geranylgeranyltransferase I inhibitors and cancer therapy: lessons from mechanism and bench-to-bedside translational studies. Oncogene 2000; 19: 6493-6584.
66. Zhang FL, Casey PJ. Protein prenylation: molecular mechanisms and functional consequences. Annu Rev Biochem 1996; 65: 241-269.
67. Sinensky M. Recent advances in the study of prenylated proteins. Biochim Biophys Acta 2000; 1484: 93-106.
68. Park HW, Boduluri SR, Moomaw JF, Casey PJ, Beese LS. Crystal structure of protein farnesyltransferase at 2.25 angstrom resolution. Science 1997; 275: 1800-1804.
69. Liang PH, Ko TP, Wang AH. Structure, mechanism and function of prenyltransferases. Eur J Biochem 2002; 269: 3339-3354.
70. Prior IA, Hancock JF. Compartmentalization of Ras proteins. J Cell Sci 2001; 114: 1603-1608.
71. Gibbs JB, Oliff A. The potential of farnesyltransferase inhibitors as cancer chemotherapeutics. Annu Rev Pharmacol Toxicol 1997; 37: 143-166.
72. Heimbrook DC, Oliff A. Therapeutic intervention and signaling. Curr Opin Cell Biol 1998; 10: 284-288.
73. Crul M, de Klerk GJ, Beijnen JH, Schellens JH. Ras biochemistry and farnesyl transferase inhibitors: a literature survey. Anticancer Drugs 2001; 12: 163-184.
74. Rowinsky EK, Windle JJ, Von Hoff DD. Ras protein farnesyltransferase: a strategic target for anticancer therapeutic development. J Clin Oncol 1999; 17: 3631-3652.
75. Tamanoi F, Gau C-L, Jiang C, Edamatsu H, Kato-Stankiewicz J. Protein farnesylation in mammalian cells: effects of farnesyltransferase inhibitors on cancer cells. Cell Mol Life Sci 2001; 58: 1636-1649.
76. Crespo NC, Ohkanda J, Yen TJ, Hamilton AD, Sebti SM. The farnesyltransferase inhibitor, FTI-2153, blocks bipolar spindle formation and chromosome alignment and causes prometaphase accumulation during mitosis of human lung cancer cells. J Biol Chem 2001; 276: 16161-16167.
77. Ashar HR, James L, Gray K, Carr D, Black S, Armstrong L et al. Farnesyl transferase inhibitors block the farnesylation of CENP-E and CENP-F and alter the association of CENP-E with the microtubules. J Biol Chem 2000; 275: 30451-30457.
78. Jiang K, Coppola D, Crespo NC, Nicosia SV, Hamilton AD, Sebti SM et al. The phosphoinositide 3-OH kinase/AKT2 pathway as a critical target for farnesyltransferase inhibitor-induced apoptosis. Mol Cell Biol 2000; 20: 139-148.
79. Kim KW, Chung HH, Chung CW, Kim IK, Miura M, Wang S et al. Inactivation of farnesyltransferase and geranylgeranyltransferase I by caspase-3: cleavage of the common alpha subunit during apoptosis. Oncogene 2001; 20: 358-366.
80. Hall A. Rho GTPases and the actin cytoskeleton. Science 1998; 279: 509-514.
81. Etienne-Manneville S, Hall A. Rho GTPases in cell biology. Nature 2002; 420: 629-635.
82. Bishop AL, Hall A. Rho GTPases and their effector proteins. Biochem J 2000; 348: 241-255.
83. Ridley AJ. Rho family proteins: coordinating cell responses. Trends Cell Biol 2001; 11: 471-477.
84. Wittmann T, Waterman-Storer CM. Cell motility: can Rho GTPases and microtubules point the way? J Cell Sci 2001; 114: 3795-3803.
85. Prendergast GC. Farnesyltransferase inhibitors: antineoplastic mechanism and clinical prospects. Curr Opin Cell Biol 2000; 12: 166-173.
86. Liu AX, Du W, Liu JP, Jessell TM, Prendergast GC. RhoB alteration is necessary for apoptotic and antineoplastic responses to farnesyltransferase inhibitors. Mol Cell Biol 2000; 20: 6105-6113.
87. Du W, Prendergast GC. Geranylgeranylated RhoB mediates suppression of human tumor cell growth by farnesyltransferase inhibitors. Cancer Res 1999; 59: 5492-5496.
88. Du W, Lebowitz PF, Prendergast GC. Cell growth inhibition by farnesyltransferase inhibitors is mediated by gain of geranylgeranylated RhoB. Mol Cell Biol 1999; 19: 1831-1840.
89. Chen Z, Sun J, Pradines A, Favre G, Adnane J, Sebti SM. Both farnesylated and geranylgeranylated RhoB inhibit malignant transformation and suppress human tumor growth in nude mice. J Biol Chem 2000; 275: 17974-17978.
90. Rowell CA, Kowalczyk JJ, Lewis MD, Garcia AM. Direct demonstration of geranylgeranylation and farnesylation of Ki-Ras in vivo. J Biol Chem 1997; 272: 14093-14097.
91. Whyte DB, Kirschmeier P, Hockenberry TN, Nunez-Oliva I, James L, Catino JJ et al. K- and N-Ras are geranylgeranylated in cells treated with farnesyl protein transferase inhibitors. J Biol Chem 1997; 272: 14459-14464.
92. Mazet JL, Padieu M, Osman H, Maume G, Mailliet P, Dereu N et al. Combination of the novel farnesyltransferase inhibitor RPR130401 and the geranylgeranyltransferase-1 inhibitor GGTI-298 disrupts MAP kinase activation and G(1)-S transition in Ki-Ras-overexpressing transformed adrenocortical cells. FEBS Lett 1999; 460: 235-240.
93. Di Paolo A, Danesi R, Caputo S, Macchia M, Lastella M, Boggi U et al. Inhibition of protein farnesylation enhances the chemotherapeutic efficacy of the novel geranylgeranyltransferase inhibitor BAL9611 in human colon cancer cells. Br J Cancer 2001; 84: 1535-1543.
94. Lobell RB, Omer CA, Abrams MT, Bhimnathwala HG, Brucker MJ, Buser CA et al. Evaluation of farnesyl:protein transferase and geranylgeranyl:protein transferase inhibitor combinations in preclinical models. Cancer Res 2001; 61: 8758-8768.
95. Lobell RB, Liu D, Buser CA, Davide JP, DePuy E, Hamilton K et al. Preclinical and clinical pharmacodynamic assessment of L-778,123, a dual inhibitor of farnesyl:protein transferase and geranylgeranyl:protein transferase type-1. Mol Cancer Ther 2002; 1: 747-758.
96. Morgan MA, Wegner J, Aydilek E, Ganser A, Reuter CWM. Synergistic cytotoxic effects in myeloid leukemia cells upon cotreatment with farnesyltransferase and geranylgeranyl transferase-I inhibitors. Leukemia (in press).
97. Huber HE, Robinson RG, Watkins A, Nahas DD, Abrams MT, Buser CA et al. Anions modulate the potency of geranylgeranyl-protein transferase I inhibitors. J Biol Chem 2001; 276: 24457-24465.
98. Lerner EC, Qian Y, Hamilton AD, Sebti SM. Disruption of oncogenic K-Ras4B processing and signaling by a potent geranylgeranyltransferase I inhibitor. J Biol Chem 1995; 270: 26770-26773.
99. Lerner EC, Zhang TT, Knowles DB, Qian Y, Hamilton AD, Sebti SM. Inhibition of the prenylation of K-Ras, but not H- or N-Ras, is highly resistant to CAAX peptidomimetics and requires both a farnesyltransferase and a geranylgeranyltransferase I inhibitor in human tumor cell lines. Oncogene 1997; 15: 1283-1288.
100. Qian Y, Vogt A, Vasudevan A, Sebti SM, Hamilton AD. Selective inhibition of type-1 geranylgeranyltransferase in vitro and in whole cells by CAAL peptidomimetics. Bioorg Med Chem 1998; 6: 293-299.
101. Vasudevan A, Qian Y, Vogt A, Blaskovich MA, Ohkanda J, Sebti SM et al. Potent, highly selective, and non-thiol inhibitors of protein geranylgeranyltransferase-I. J Med Chem 1999; 42: 1333-1340.
102. Buser CA, Dinsmore CJ, Fernandes C, Greenberg I, Hamilton K, Mosser SD et al. High-performance liquid chromatography/mass spectrometry characterization of Ki4B-Ras in PSN-1 cells treated with the prenyltransferase inhibitor L-778,123. Anal Biochem 2001; 290: 126-137.
103. Sun J, Qian Y, Hamilton AD, Sebti SM. Both farnesyltransferase and geranylgeranyltransferase I inhibitors are required for inhibition of oncogenic K-Ras prenylation but each alone is sufficient to suppress human tumor growth in nude mouse xenografts. Oncogene 1998; 16: 1467-1473.
104. Sun J, Blaskovich MA, Knowles D, Qian Y, Ohkanda J, Bailey RD et al. Antitumor efficacy of a novel class of non-thiol-containing peptidomimetic inhibitors of farnesyltransferase and geranylgeranyltransferase I: combination therapy with the cytotoxic agents cisplatin, Taxol, and gemcitabine. Cancer Res 1999; 59: 4919-4926.
105. Miquel K, Pradines A, Sun J, Qian Y, Hamilton AD, Sebti SM et al. GGTI-298 induces G0-G1 block and apoptosis whereas FTI-277 causes G2-M enrichment in A549 cells. Cancer Res 1997; 57: 1846-1850.
106. Vogt A, Sun J, Qian Y, Hamilton AD, Sebti SM. The geranylgeranyltransferase-I inhibitor GGTI-298 arrests human tumor cells in G0/G1 and induces p21(WAF1/CIP1/SDI1) in a p53-independent manner. J Biol Chem 1997; 272: 27224-27229.
107. Adnane J, Bizouarn FA, Qian Y, Hamilton AD, Sebti SM. p21(WAF1/CIP1) is upregulated by the geranylgeranyltransferase I inhibitor GGTI-298 through a transforming growth factor beta-and Sp1 -responsive element: involvement of the small GTPase rhoA. Mol Cell Biol 1998; 18: 6962-6970.
108. Thompson GR, Naoumova RP. Novel lipid-regulating drugs. Expert Opin Invest Drugs 2000; 9: 2619-2628.
109. Wong WW, Dimitroulakos J, Minden MD, Penn LZ. HMG-CoA reductase inhibitors and the malignant cell: the statin family of drugs as triggers of tumor-specific apoptosis. Leukemia 2002; 16: 508-519.
110. Jakobisiak M, Bruno S, Skierski JS, Darzynkiewicz Z. Cell cycle-specific effects of lovastatin. Proc Natl Acad Sci USA 1991; 88: 3628-3632.
111. Keyomarsi K, Sandoval L, Band V, Pardee AB. Synchronization of tumor and normal cells from G1 to multiple cell cycles by lovastatin. Cancer Res 1991; 51: 3602-3609.
112. Gray-Bablin J, Rao S, Keyomarsi K. Lovastatin induction of cyclin-dependent kinase inhibitors in human breast cells occurs in a cell cycle-independent fashion. Cancer Res 1997; 57: 604-609.
113. Lee SJ, Ha MJ, Lee J, Nguyen P, Choi YH, Pirnia F et al. Inhibition of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase pathway induces p53-independent transcriptional regulation of p21 (WAF1/CIP1) in human prostate carcinoma cells. J Biol Chem 1998; 273: 10618-10623.
114. Rao S, Lowe M, Herliczek TW, Keyomarsi K. Lovastatin mediated G1 arrest in normal and tumor breast cells is through inhibition of CDK2 activity and redistribution of p21 and p27, independent of p53. Oncogene 1998; 17: 2393-2402.
115. Wachtershauser A, Akoglu B, Stein J. HMG-CoA reductase inhibitor mevastatin enhances the growth inhibitory effect of butyrate in the colorectal carcinoma cell line Caco-2. Carcinogenesis 2001; 22: 1061-1067.
116. Dimitroulakos J, Thai S, Wasfy GH, Hedley DW, Minden MD, Penn LZ. Lovastatin induces a pronounced differentiation response in acute myeloid leukemias. Leukemia Lymphoma 2000; 40: 167-178.
117. Wong WW, Tan MM, Xia Z, Dimitroulakos J, Minden MD, Penn LZ. Cerivastatin triggers tumor-specific apoptosis with higher efficacy than lovastatin. Clin Cancer Res 2001; 7: 2067-2075.
118. Newman A, Clutterbuck RD, Powles RL, Millar JL. Selective inhibition of primary acute myeloid leukaemia cell growth by lovastatin. Leukemia 1994; 8: 274-280.
119. Newman A, Clutterbuck RD, DeLord C, Powles RL, Catovsky D, Millar JL. The sensitivity of leukemic bone marrow to simvastatin is lost at remission: a potential purging agent for autologous bone marrow transplantation. J Invest Med 1995; 43: 269-274.
120. Newman A, Clutterbuck RD, Powles RL, Catovsky D, Millar JL. A comparison of the effect of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors simvastatin, lovastatin and pravastatin on leukaemic and normal bone marrow progenitors. Leukemia Lymphoma 1997; 24: 533-537.
121. Dimitroulakos J, Nohynek D, Backway KL, Hedley DW, Yeger H, Freedman MH et al. Increased sensitivity of acute myeloid leukemias to lovastatin-induced apoptosis: a potential therapeutic approach. Blood 1999; 93: 1308-1318.
122. Wang IK, Lin-Shiau SY, Lin JK. Induction of apoptosis by lovastatin through activation of caspase-3 and DNase II in leukaemia HL-60 cells. Pharmacol Toxicol 2000; 86: 83-91.
123. Marcelli M, Cunningham GR, Haidacher SJ, Padayatty SJ, Sturgis L, Kagan C et al. Caspase-7 is activated during lovastatin-induced apoptosis of the prostate cancer cell line LNCaP. Cancer Res 1998; 58: 76-83.
124. Xia Z, Tan MM, Wong WW, Dimitroulakos J, Minden MD, Penn LZ. Blocking protein geranylgeranylation is essential for lovastatin-induced apoptosis of human acute myeloid leukemia cells. Leukemia 2001; 15: 1398-1407.
125. Lishner M, Bar-Sef A, Elis A, Fabian I. Effect of simvastatin alone and in combination with cytosine arabinoside on the proliferation of myeloid leukemia cell lines. J Invest Med 2001; 49: 319-324.
126. Stirewalt DL, Appelbaum FR, Willman CL, Zager RA, Banker DE. Mevastatin can increase toxicity in primary AMLs exposed to standard therapeutic agents, but statin efficacy is not simply associated with ras hotspot mutations or overexpression. Leukemia Res 2003; 27: 133-145.
127. Clutterbuck RD, Millar BC, Powles RL, Newman A, Catovsky D, Jarman M et al. Inhibitory effect of simvastatin on the proliferation of human myeloid leukaemia cells in severe combined immunodeficient (SCID) mice. Br J Haematol 1998; 102: 522-527.
128. Minden MD, Dimitroulakos J, Nohynek D, Penn LZ. Lovastatin induced control of blast cell growth in an elderly patient with acute myeloblastic leukemia. Leukemia Lymphoma 2001; 40: 659-662.
129. Li HY, Appelbaum FR, Willman CL, Zager RA, Banker DE. Cholesterol modulating agents kill acute myeloid leukemia cells and sensitize them to therapeutics by blocking adaptive cholesterol responses. Blood 2003; 101: 3628-3634.
130. Haluska P, Dy GK, Adjei AA. Farnesyl transferase inhibitors as anticancer agents. Eur J Cancer 2002; 38: 1685-1700.
131. End DW, Smets G, Todd AV, Applegate TL, Fuery CJ, Angibaud P et al. Characterization of the antitumor effects of the selective farnesyl protein transferase inhibitor R115777 in vivo and in vitro. Cancer Res 2001; 61: 131-137.
132. Kelland LR, Smith V, Valenti M, Patterson L, Clarke PA, Detre S et al. Preclinical antitumor activity and pharmacodynamic studies with the farnesyl protein transferase inhibitor R115777 in human breast cancer. Clin Cancer Res 2001; 7: 3544-3550.
133. Zujewski J, Horak ID, Bol CJ, Woestenborghs R, Bowden C, End DW et al. Phase I and pharmacokinetic study of farnesyl protein transferase inhibitor R115777 in advanced cancer. J Clin Oncol 2000; 18: 927-941.
134. Karp JE, Lancet JE, Kaufmann SH, End DW, Wright JJ, Bol K 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.
135. Punt CJ, van Maanen L, Bol CJ, Seifert WF, Wagener DJ. Phase I and pharmacokinetic study of the orally administered farnesyl transferase inhibitor R115777 in patients with advanced solid tumors. Anticancer Drugs 2001; 12: 193-197.
136. Crul M, de Klerk GJ, Swart M, van't Veer LJ, de Jong D, Boerrigter L et al. Phase I clinical and pharmacologic study of chronic oral administration of the farnesyl protein transferase inhibitor R115777 in advanced cancer. J Clin Oncol 2002; 20: 2726-2735.
137. 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.
138. Cortes JE, Albitar M, Thomas D, Giles F, Kurzrock R, Thibault A et al. Efficacy of the farnesyl transferase inhibitor R115777 in chronic myeloid leukemia and other hematological malignancies. Blood 2003; 101: 1692-1697.
139. Bishop WR, Bond R, Petrin J, Wang L, Patton R, Doll R et al. Novel tricyclic inhibitors of farnesyl protein transferase. J Biol Chem 1995; 270: 30611-30618.
140. Liu M, Bryant MS, Chen J, Lee S, Yaremko B, Lipari P et al. Antitumor activity of SCH 66336, an orally bioavailable tricyclic inhibitor of farnesyl protein transferase, in human tumor xenograft models and wap-ras transgenic mice. Cancer Res 1998; 58: 4947-4956.
141. Petit T, Izbicka E, Lawrence RA, Bishop WR, Weitman S, Von Hoff DD. Activity of SCH 66336, a tricyclic farnesyltransferase inhibitor, against human tumor colony-forming units. Ann Oncol 1999; 10: 449-453.
142. Liu M, Bishop WR, Nielsen LL, Bryant MS, Kirschmeier P. Orally bioavailable farnesyltransferase inhibitors as anticancer agents in transgenic and xenograft models. Methods Enzymol 2001; 333: 306-318.
143. Shi B, Yaremko B, Hajian G, Terracina G, Bishop WR, Liu M et al. The farnesyl protein transferase inhibitor SCH66336 synergizes with taxanes in vitro and enhances their antitumor activity in vivo. Cancer Chemother Pharmacol 2000; 46: 387-393.
144. Adjei AA, Davis JN, Bruzek LM, Erlichman C, Kaufmann SH. Synergy of the protein farnesyltransferase inhibitor SCH66336 and cisplatin in human cancer cell lines. Clin Cancer Res 2001; 7: 1438-1445.
145. Peters DG, Hoover RR, Gerlach MJ, Koh EY, Zhang H, Choe K et al. Activity of the farnesyl protein transferase inhibitor SCH66336 against BCR/ABL-induced murine leukemia and primary cells from patients with chronic myeloid leukemia. Blood 2001; 97: 1404-1412.
146. Reichert A, Heisterkamp N, Daley GQ, Groffen J. Treatment of Bcr/Abl-positive acute lymphoblastic leukemia in P190 transgenic mice with the farnesyl transferase inhibitor SCH66336. Blood 2001; 97: 1399-1403.
147. Hoover RR, Mahon FX, Melo JV, Daley GQ. Overcoming STI571 resistance with the farnesyl transferase inhibitor SCH66336. Blood 2002; 100: 1068-1071.
148. Brodsky AL, Daley GQ, Hoover RR, Carr D, Kirschmeier P. Apoptotic synergism between STI571 and the farnesyl transferase inhibitor SCH66336 on an imatinib-sensitive cell line. Blood 2003; 101: 2070.
149. Adjei AA, Erlichman C, Davis JN, Cutler DL, Sloan JA, Marks RS et al. A Phase I trial of the farnesyl transferase inhibitor SCH66336: evidence for biological and clinical activity. Cancer Res 2000; 60: 1871-1877.
150. Eskens FA, Awada A, Cutler DL, de Jonge MJ, Luyten GP, Faber MN et al. Phase I and pharmacokinetic study of the oral farnesyl transferase inhibitor SCH 66336 given twice daily to patients with advanced solid tumors. J Clin Oncol 2001; 19: 1167-1175.
151. Hunt JT, Ding CZ, Batorsky R, Bednarz M, Bhide R, Cho Y et al. Discovery of (R)-7-cyano-2,3,4,5-tetrahydro-1-(1H-imidazol-4-ylmethyl) -3-(phenylmethyl)-4-(2-thienylsulfonyl)-1 H-1,4-benzodiazepine (BMS-214662), a farnesyltransferase inhibitor with potent preclinical antitumor activity. J Med Chem 2000; 43: 3587-3595.
152. Rose WC, Lee FY, Fairchild CR, Lynch M, Monticello T, Kramer RA, Manne V. Preclinical antitumor activity of BMS-214662, a highly apoptotic and novel farnesyltransferase inhibitor. Cancer Res 2001; 61: 7507-7517.
153. Britten CD, Rowinsky EK, Soignet S, Patnaik A, Yao SL, Deutsch P et al. A phase I and pharmacological study of the farnesyl protein transferase inhibitor L-778,123 in patients with solid malignancies. Clin Cancer Res 2001; 7: 3894-3903.
154. Hahn SM, Bernhard EJ, Regine W, Mohiuddin M, Haller DG, Stevenson JP et al. A Phase I trial of the farnesyltransferase inhibitor L-778,123 and radiotherapy for locally advanced lung and head and neck cancer. Clin Cancer Res 2002; 8: 1065-1072.
155. Nagasu T, Yoshimatsu K, Rowell C, Lewis MD, Garcia AM. Inhibition of human tumor xenograft growth by treatment with the farnesyl transferase inhibitor B956. Cancer Res 1995; 55: 5310-5314.
156. James G, Goldstein JL, Brown MS. Resistance of K-RasBV12 proteins to farnesyltransferase inhibitors in Rat1 cells. Proc Natl Acad Sci USA 1996; 93: 4454-4458.
157. Kohl NE, Omer CA, Conner MW, Anthony NJ, Davide JP, deSolms SJ et al. Inhibition of farnesyltransferase induces regression of mammary and salivary carcinomas in ras transgenic mice. Nat Med 1995; 1: 792-797.
158. Mangues R, Corral T, Kohl NE, Symmans WF, Lu S, Malumbres M et al. Antitumor effect of a farnesyl protein transferase inhibitor in mammary and lymphoid tumors overexpressing N-ras in transgenic mice. Cancer Res 1998; 58: 1253-1259.
159. Omer CA, Chen Z, Diehl RE, Conner MW, Chen HY, Trumbauer ME et al. Mouse mammary tumor virus-Ki-rasB transgenic mice develop mammary carcinomas that can be growth-inhibited by a farnesyl:protein transferase inhibitor. Cancer Res 2000; 60: 2680-2688.
160. Zhang FL, Kirschmeier P, Carr D, James L, Bond RW, Wang L et al. Characterization of Ha-ras, N-ras, Ki-Ras4A, and Ki-Ras4B as in vitro substrates for farnesyl protein transferase and geranylgeranyl protein transferase type 1. J Biol Chem 1997; 272: 10232-10239.
161. Kato K, Cox AD, Hisaka MM, Graham SM, Buss JE, Der CJ. Isoprenoid addition to Ras protein is the critical modification for its membrane association and transforming activity. Proc Natl Acad Sci USA 1992; 89: 6403-6407.
162. Prendergast GC, Davide JP, Lebowitz PF, Wechsler-Reya R, Kohl NE. Resistance of a variant ras-transformed cell line to phenotypic reversion by farnesyl transferase inhibitors. Cancer Res 1996; 56: 2626-2632.
163. Del Villar K, Urano J, Guo L, Tamanoi F. A mutant form of human protein farnesyltransferase exhibits increased resistance to farnesyltransferase inhibitors. J Biol Chem 1999; 274: 27010-27017.
164. Smith V, Rowlands MG, Barrie E, Workman P, Kelland LR.
165. Hu W, Wu W, Yeung SC, Freedman RS, Kavanagh JJ, Verschraegen CF. Increased expression of heat shock protein 70 in adherent ovarian cancer and mesothelioma following treatment with manumycin, a farnesyl transferase inhibitor. Anticancer Res 2002; 22: 665-672.
166. Sepp-Lorenzino L, Ma Z, Rands E, Kohl NE, Gibbs JB, Oliff et al. A peptidomimetic inhibitor of farnesyl:protein transferase blocks the anchorage-dependent and -independent growth of human tumor cell lines. Cancer Res 1995; 55: 5302-5309.
167. Wang E, Casciano CN, Clement RP, Johnson WW. The farnesyl protein transferase inhibitor SCH66336 is a potent inhibitor of MDR1 product P-glycoprotein. Cancer Res 2001; 61: 7525-7529.
168. Bos JL, Verlaan-de-Vries M, van-der-Eb AJ, Janssen JW, Delwel R, Lowenberg B et al. Mutations in N-Ras predominate in acute myeloid leukemia. Blood 1987; 69: 1237-1241.
169. Janssen J, Steenvoorden A, Lyons J, Anger B, Bohlke JU, Bos JL 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.
170. Schaich M, Ritter M, Illmer T, Lisske P, Thiede C, Schakel U et al. Mutations in ras proto-oncogenes are associated with lower mdr1 gene expression in adult acute myeloid leukaemia. Br J Haematol 2001; 112: 300-307.
171. Farr CJ, Saiki RK, Erlich HA, McCormick F, Marshall CJ. Analysis of Ras gene mutations in acute myeloid leukemia by polymerase chain reaction and oligonucteotide probes. Proc Natl Acad Sci USA 1988; 85: 1629-1633.
172. Vogelstein B, Civin CI, Preisinger AC, Krischer JP, Steuber P, Ravindranath Y et al. Ras gene mutations in childhood acute myeloid leukemia: a pediatric oncology group study. Genes Chromosomer Cancer 1990; 2: 159-162.
173. Neri A, Knowes DM, Greco A, McCormick F, Dalla-Favera R. Analysis of Ras oncogene mutations in human lymphoid malignancies. Proc Natl Acad Sci USA 1988; 85: 9268-9272.
174. Browett PJ, Yaxley JC, Norton JD. Activation of Harvey ras oncogene by mutation at codon 12 is very rare in hematopoietic malignancies. Leukemia 1989; 3: 86-88.
175. Browett PJ, Norton JD. Analysis of RAS gene mutations and methylation state in human leukemias. Oncogene 1989; 4: 1029-1036.
176. Padua RA, Carter G, Hughes D, Gow J, Farr C, Oscier D et al. Ras mutations in myelodysplasia detected by amplification, oligonucleotide hybridization and transformation. Leukemia 1988; 2: 503-510.
177. Hirsch-Ginsberg C, LeMaistre AC, Kantarjian H, Talpaz M, Cork A, Freireich EJ et al. Ras mutations are rare events in Philadelphia chromosome-negative/bcr gene rearrangement-negative chronic myelogenous leukemia, but are prevalent in chronic myelomonocytic leukemia. Blood 1990; 76: 1214-1219.
178. Neri A, Murphy JP, Cro L, Ferrero D, Tarella C, Baldini L et al. Ras oncogene mutation in multiple myeloma. J Exp Med 1989; 170: 1715-1725.
179. Tanaka K, Takechi M, Asaoku H, Dohy H, Kamada N. A high frequency of N-Ras oncogene mutations in multiple myeloma. Int J Hematol 1992; 56: 119-127.
180. Corradini P, Ladetto M, Voena C, Palumbo A, Inghirami G, Knowles DM et al. Mutational activation of N- and K-RAS oncogenes in plasma cell dyscrasias. Blood 1993; 81: 2708-2713.
181. Hallek M, Leif Bergsagel P, Anderson KC. Multiple myeloma: increasing evidence for a multistep transformation process. Blood 1998; 91: 3-21.
182. Bezieau S, Devilder MC, Avet-Loiseau H, Mellerin MP, Puthier D, Pennarun E et al. High incidence on N and K-Ras activating mutations in multiple myeloma and primary plasma cell leukemia at diagnosis. Hum Mutat 2001; 18: 212-224.
183. Kalakonda N, Rothwell DG, Scarffe JH, Norton JD. Detection of N-Ras codon 61 mutations in subpopulations of tumor cells in multiple myeloma at presentation. Blood 2001; 98: 1555-1560.
184. Padua RA, Guinn BA, Al-Sabah AI, Smith M, Taylor C, Pettersson T et al. Ras, FMS and p53 mutations and poor clinical outcome in myelodysplasias: a 10-year follow-up. Leukemia 1998; 12: 887-892.
185. Stirewalt DL, Kopecky KJ, Meshinchi S, Appelbaum FR, Slovak ML, Willman CL et al. FLT3, RAS, and TP53 mutations in elderly patients with acute myeloid leukemia. Blood 2001; 97: 3589-3595.
186. Yamamoto Y, Kiyoi H, Nakano Y, Suzuki R, Kodera Y, Miyawaki S et al. Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies. Blood 2001; 97: 2434-2439.
187. 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: 938-983.
188. Gilliland DG, Griffin JD. Role of FLT3 in leukemia. Curr Opin Hematol 2002; 9: 274-281.
189. Thiede C, Steudel C, Mohr B, Schaich M, Schakel U, Platzbecker U 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.
190. Nagata H, Worobec AS, Oh CK, Chowdhury BA, Tannenbaum S, Suzuki Y et al. Identification of a point mutation in the catalytic domain of the protooncogene c-kit in peripheral blood mononuclear cells of patients who have mastocytosis with an associated hematologic disorder. Proc Natl Acad Sci USA 1995; 92: 10560-10564.
191. Buttner C, Henz BM, Welker P, Sepp NT, Grabbe J. Identification of activating c-kit mutations in adult-, but not in childhood-onset indolent mastocytosis: a possible explanation for divergent clinical behavior. J Invest Dermatol 1998; 111: 1227-1231.
192. Cazzaniga G, Tosi S, Aloisi A, Giudici G, Daniotti M, Pioltelli P et al. The tyrosine kinase abl-related gene ARG is fused to ETV6 in an AML-M4Eo patient with a t(1;12)(q25;p13): molecular cloning of both reciprocal transcripts. Blood 1999; 94: 4370-4373.
193. Iijima Y, Ito T, Oikawa T, Eguchi M, Euchi-Ishimae M, Kamada N et al. A new ETV/TEL partner gene, ARG (ABL-related gene or ABL2), identified in an AML-M3 cell line with a t(1;12)(q25;p13) translocation. Blood 2000; 95: 2126-2131.
194. Eguchi M, Eguchi-Ishimae M, Tojo A, Morishita K, Suzuki K, Sato Y et al. Fusion of ETV6 to neurotrophin-3 receptor TRKC in acute myeloid leukemia with t(12;15)(p13;q25). Blood 1999; 93: 1355-1363.
195. Liu Q, Schwaller J, Kutok J, Cain D, Aster JC, Williams IR et al. Signal transduction and transforming properties of the TEL-TRKC fusions associated with t(12;15)(p13;q25) in congenital fibrosarcoma and acute myelogenous leukemia. EMBO J 2000; 19: 1827-1838.
196. Abe A, Emi N, Tanimoto M, Terasaki H, Marunouchi T, Saito H. Fusion of the platelet-derived growth factor beta to a novel gene CEV14 in acute myelogenous leukemia after clonal evolution. Blood 1997; 90: 4271-4277.
197. Elmberger FG, Lozano MD, Weisenburger DD, Sanger W, Chan WC. Transcripts of the npm-alk fusion gene in anaplastic large cell lymphoma Hodgkin's disease, and reactive lymphoid lesions. Blood 1995; 86: 3517-3521.
198. Waggott W, Lo YM, Bastard C, Gatter KC, Leroux D, Mason DY et al. Detection of NPM-ALK DNA rearrangement in CD30 positive anaplastic large cell lymphoma. Br J Haematol 1995; 89: 905-907.
199. Zou X, Calame K. Signaling pathways activated by oncogenic forms of Abl tyrosine kinase. J Biol Chem 1999; 274: 18141-18144.
200. Demiroglu A, Steer E, Heath C, Taylor K, Bentley M, Allen S et al. The t(8;22) in chronic myeloid leukemia fuses BCR to FGFR1: transforming activity and specific inhibition of FGFR1 fusion proteins. Blood 2001; 98: 3778-3783.
201. Ross TS, Bernard OA, Berger R, Gilliland DG. Fusion of Huntingtin interacting protein 1 to platelet-derived growth factor beta receptor (PDGFbetaR) in chronic myelomonocytic leukemia with t(5;7)(q33;q11.2). Blood 1998; 91: 4419-4426.
202. Ross TS, Gilliland DG. Transforming properties of the Huntingtin interacting protein 1/platelet-derived growth factor beta receptor fusion protein. J Biol Chem 1999; 274: 22328-22336.
203. Sohal J, Chase A, Mould S, Corcoran M, Oscier D, Iqbal S et al. Identification of four new translocations involving FGFR1 in myeloid disorders. Genes Chromosomes Cancer 2001; 32: 155-163.
204. Macdonald D, Reiter A, Cross NC. The 8p11 myeloproliferative syndrome: a distinct clinical entity caused by constitutive activation of FGFR1. Acta Haematol 2002; 107: 101-107.
205. Tycko B, Smith SD, Sklar J. Chromosomal translocations joining LCK and TCRB loci in human T cell leukemia. J Exp Med 1991; 174: 867-873.
206. Burnett RC, Thirman MJ, Rowley JD, Diaz MO. Molecular analysis of the T-cell acute lymphoblastic leukemia-associated t(1;7)(p34;q34) that fuses LCK and TCRB. Blood 1994; 84: 1232-1236.
207. Lacronique V, Boureux A, Monni R, Dumon S, Mauchauffe M, Mayeux P et al. Transforming properties of chimeric TEL-JAK proteins in Ba/F3 cells. Blood 2000; 95: 2076-2083.
208. Side L, Taylor B, Cayouette M, Conner E, Thompson P, Luce M et al. Homozygous inactivation of the NF-1 gene in bone marrow cells from children with neurofibromatosis type 1 and malignant myeloid disorders. N Engl J Med 1997; 336: 1713-1720.
209. Farnsworth CC, Seabra MC, Ericsson LH, Gelb MH, Glomset JA. Rab geranylgeranyl transferase catalyzes the geranylgeranylation of adjacent cysteines in the small GTPases Rab1A, Rab3A, and Rab5A. Proc Natl Acad Sci USA 1994; 91: 11963-11967.
210. Lebowitz PF, Prendergast GC. Non-Ras targets of farnesyltransferase inhibitors: focus on Rho. Oncogene 1998; 17: 1439-1445.
211. Farnsworth CC, Wolda SL, Gelb MH, Glomset JA. Human lamin B contains a farnesylated cysteine residue. J Biol Chem 1989; 264: 20422-20429.
212. James GL, Goldstein JL, Pathak RK, Anderson RG, Brown MS. PxF, a prenylated protein of peroxisomes. J Biol Chem 1994; 269: 14182-14190.
213. Lai RK, Perez-Sala D, Canada FJ, Rando RR. The gamma subunit of transducin is farnesylated. Proc Natl Acad Sci USA 1990; 87: 7673-7677.
214. Inglese J, Glickman JF, Lorenz W, Caron MG, Lefkowitz RJ. Isoprenylation of a protein kinase Requirement of farnesylation/alpha-carboxyl methylation for full enzymatic activity of rhodopsin kinase. J Biol Chem 1992; 267: 1422-1425.
215. AnantJS, Ong OC, Xie HY, Clarke S, O'Brien PJ, Fung BK. In vivo differential prenylation of retinal cyclic GMP phosphodiesterase catalytic subunits. J Biol Chem 1992; 267: 687-690.
216. Heilmeyer Jr LM, Serwe M, Weber C, Metzger J, Hoffmann-Posorske E, Meyer HE. Farnesylcysteine, a constituent of the alpha and beta subunits of rabbit skeletal muscle phosphorylase kinase: localization by conversion to S-ethylcysteine and by tandem mass spectrometry. Proc Natl Acad Sci USA 1992; 89: 9554-9558.