Farnesyltransferase inhibitor tipifarnib inhibits rheb prenylation and stabilizes bax in acute myelogenous leukemia cells

Haematologica

Volumn 99, Issue 1, 2014, Pages 60-69

  Ding, Husheng ^a   Mcdonald, Jennifer S ^a   Yun, Seongseok ^a,b   Schneider, Paula A ^a   Peterson, Kevin L ^a   Flatten, Karen S ^a   Loegering, David A ^a   Oberg, Ann L ^b   Riska, Shaun M ^b   Huang, Shengbing ^c   Sinicrope, Frank A ^c   Adjei, Alex A ^d   Karp, Judith E ^e   Meng, X Wei ^a   Kaufmann, Scott H ^a,b  

^a Division of Oncology Research   (United States)

^b Department of Molecular Pharmacology and Experimental Therapeutics ^*  (United States)

^c Mayo Clinic   (United States)

^d ROSWELL PARK CANCER INSTITUTE   (United States)

^e JOHNS HOPKINS UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENTS; APOPTOSIS; APOPTOSIS REGULATORY PROTEINS; BCL-2-ASSOCIATED X PROTEIN; CELL LINE, TUMOR; CELL PROLIFERATION; DRUG RESISTANCE, NEOPLASM; FARNESYLTRANSTRANSFERASE; HUMANS; LEUKEMIA, MYELOID, ACUTE; MONOMERIC GTP-BINDING PROTEINS; NEUROPEPTIDES; PRENYLATION; PROTEIN STABILITY; PROTO-ONCOGENE PROTEINS; QUINOLONES; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES; U937 CELLS;

EID: 84892603452     PISSN: 03906078     EISSN: 15928721     Source Type: Journal    
DOI: 10.3324/haematol.2013.087734     Document Type: Article

References (50)

1. Karp JE, Lancet JE. Development of farnesyl-transferase inhibitors for clinical cancer therapy: focus on hematologic malignancies. Cancer Invest. 2007;25(6):484-494.
2. Harousseau JL. Farnesyltransferase ini-hibitors in hematologic malignancies. Blood Rev. 2007;21(4):173-182.
3. Stone RM. Targeted agents in AML: much more to do. Best Pract Res Clin Haematol. 2007;20(1):39-48.
4. Doll RJ, Kirschmeier P, Bishop WR. Farnesyltransferase inhibitors as anticancer agents: critical crossroads. Curr Opin Drug Discov Devel. 2004;7(4):478-486.
5. Witzig TE, Tang H, Micallef IM, Ansell SM, Ding H, Link BK, et al. A Multi-Institution Phase 2 Study of the Farnesyltransferase Inhibitor Tipifarnib (R115777) in Patients with Relapsed and Refractory Lymphomas. Blood. 2011;118:4882-4889.
6. Lancet JE, Gojo I, Gotlib J, Feldman EJ, Greer J, Liesveld JL, et al. A phase 2 study of the farnesyltransferase inhibitor tipifarnib in poor-risk and elderly patients with previously untreated acute myelogenous leukemia. Blood. 2007;109(4):1387-1394.
7. Harousseau JL, Martinelli G, Jedrzejczak WW, Brandwein JM, Bordessoule D, Masszi T, et al. A randomized phase 3 study of tipi-farnib compared with best supportive care, including hydroxyurea, in the treatment of newly diagnosed acute myeloid leukemia in patients 70 years or older. Blood. 2009;114 (6):1166-1173.
8. Luger S, Zicki L, Paietta E, Ketterling R P, Litzow MR, Rowe JM, et al. R115777(tipi-farnib) Improves Early Survival when Used As Maintenance Therapy for Elderly or Relapsed/Refractory Patients with Acute Myelogenous Leukemia in Remission. Blood (ASH Annual Meeting Abstracts). 2012;120((ASH Annual Meeting Abstracts)): 676.
9. Kaufmann SH, Earnshaw WC. Induction of apoptosis by cancer chemotherapy. Exp Cell Res. 2000;256:42-49.
10. Johnstone RW, Ruefli AA, Lowe SW. Apoptosis. A Link Between Cancer Genetics and Chemotherapy. Cell. 2002;108(2):153-164.
11. Chipuk JE, Green DR. How do BCL-2 proteins induce mitochondrial outer membrane permeabilization? Trends Cell Biol. 2008; 18(4):157-164.
12. Martinou JC, Youle RJ. Mitochondria in apoptosis: Bcl-2 family members and mito-chondrial dynamics. Dev Cell. 2011;21 (1):92-101.
13. Strasser A, Cory S, Adams JM. Deciphering the rules of programmed cell death to improve therapy of cancer and other diseases. EMBO J. 2011;30(18):3667-3683.
14. Taylor RC, Cullen SP, Martin SJ. Apoptosis: controlled demolition at the cellular level. Nat Rev Mol Cell Biol. 2008;9(3):231-241.
15. Dai H, Smith A, Meng XW, Schneider PA, Pang Y-P, Kaufmann SH. Transient Binding of an Activator BH3 Domain to the Bak BH3-Binding Groove Initiates Bak Oligomerization. J Cell Biol. 2011;194:39-48.
16. Ding H, Hackbarth J, Schneider PA, Lee S-H, Meng XW, Dai H, et al. Cytotoxicity of Farnesyltransferase Inhibitors in Lymphoid Cells Mediated by MAPK Pathway Inhibition and Bim Upregulation. Blood. 2011;(118):4872-4881.
17. Ebinu JO, Bottorff DA, Chan EY, Stang SL, Dunn RJ, Stone JC. RasGRP, a Ras guanyl nucleotide-releasing protein with calcium-and diacylglycerol-binding motifs. Science. 1998;280(5366):1082-1086.
18. Raponi M, Lancet JE, Fan H, Dossey L, Lee G, Gojo I, et al. A 2-gene classifier for predicting response to the farnesyltransferase inhibitor tipifarnib in acute myeloid leukemia. Blood. 2008;111(5):2589-2596.
19. Lancet JE, Feldman E, Goster MC, Gojo I, Odenike O, Komrokji RS, et al. Phase 2 Trial of the Farnesyltransferase Inhibitor Tipifarnib in Previously Untreated Older Adults with AML and Baseline Presence of a Specific 2-Gene Expression Signature Ratio. Blood (ASH Annual Meeting Abstracts). 2012;120(ASH Annual Meeting Abstracts):1508.
20. Clark GJ, Kinch MS, Rogers-Graham K, Sebti SM, Hamilton AD, Der CJ. The Ras-related protein Rheb is farnesylated and antagonizes Ras signaling and transformation. J Biol Chem. 1997;272(16):10608-10615.
21. Basso AD, Mirza A, Liu G, Long BJ, Bishop WR, Kirschmeier P. The farnesyl transferase inhibitor (FTI) SCH66336 (lonafarnib) inhibits Rheb farnesylation and mTOR signaling. Role in FTI enhancement of taxane and tamoxifen anti-tumor activity. J Biol Chem. 2005;280(35):31101-31108.
22. Mavrakis KJ, Zhu H, Silva RL, Mills JR, Teruya-Feldstein J, Lowe SW, et al. Tumorigenic activity and therapeutic inhibition of Rheb GTPase. Genes Dev. 2008; 22(16):2178-2188.
23. Karp JE, Flatten K, Feldman EJ, Greer JM, Loegering DA, Ricklis RM, et al. Active oral regimen for elderly adults with newly diagnosed acute myelogenous leukemia: a pre-clinical and phase 1 trial of the farnesyltrans-ferase inhibitor tipifarnib (R115777, Zarnestra) combined with etoposide. Blood. 2009;113(20):4841-4852.
24. Caserta TM, Smith AN, Gultice AD, Reedy MA, Brown TL. Q-VD-OPh, a broad spectrum caspase inhibitor with potent anti-apoptotic properties. Apoptosis. 2003;8(4): 345-352.
25. Huang S, Okumura K, Sinicrope FA. BH3 mimetic obatoclax enhances TRAIL-mediated apoptosis in human pancreatic cancer cells. Clin Cancer Res. 2009;15(1):150-159.
26. Meng XW, Peterson KL, Dai H, Schneider P, Lee SH, Zhang JS, et al. High cell surface death receptor expression determines type I versus type II signaling. J Biol Chem. 2011;286:35823-35833.
27. Lancet JE, Gojo I, Gotlib J, Feldman EJ, Greer J, Liesveld JL, et al. A phase 2 study of the farnesyltransferase inhibitor tipifarnib in poor-risk and elderly patients with previously untreated acute myeloid leukemia. Blood. 2006;109:1387-1394.
28. Karp JE, Vener TI, Raponi M, Flatten K, Greer JM, Smith BD, et al. Multi-Institution Phase II Clinical and Pharmacogenomic Trial of Tipifarnib Plus Etoposide for Elderly Adults with Newly Diagnosed Acute Myelogenous Leukemia. Blood. 2012;119: 55-63.
29. Kaufmann SH, Svingen PA, Gore SD, Armstrong DK, Cheng Y-C, Rowinsky EK. Altered Formation of Topotecan-Stabilized Topoisomerase I-DNA Adducts in Human Leukemia Cells. Blood. 1997;89:2098-2104.
30. Kaufmann SH. Reutilization of Immunoblots After Chemiluminescent Detection. Analytical Biochemistry. 2001; 296:283-286.
31. Mesa RA, Loegering D, Powell HL, Flatten K, Arlander SAH, Dai NT, et al. Heat Shock Protein 90 Inhibition Sensitizes Acute Myelogenous Leukemia Cells to Cytarabine. Blood. 2005;106:318-327.
32. Meng XW, Lee SH, Dai H, Loegering D, Yu C, Flatten K, et al. Mcl-1 as a buffer for proapoptotic Bcl-2 family members during TRAIL-induced apoptosis: a mechanistic basis for sorafenib (Bay 43-9006)-induced TRAIL sensitization. J Biol Chem. 2007;282(41):29831-29846.
33. Wu Z. A model-based background adjustment for oligonucleotide expression arrays. J Am Stat Assoc. 2004;99: 909-917.
34. Ballman KV, Grill DE, Oberg AL, Therneau TM. Faster cyclic loess: normalizing RNA arrays via linear models. Bioinformatics. 2004;20(16):2778-2786.
35. Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U, et al. Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics. 2003;4(2):249-264.
36. Smyth GK. Linear models and empirical Bayes methods for assessing differential expression in microarray experiments. Statistical Applications in Genetics and Molecular Biology. 2004;3(1):Article 1.
37. Lamb J, Crawford ED, Peck D, Modell JW, Blat IC, Wrobel MJ, et al. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease. Science. 2006;313(5795):1929-1935.
38. Karp JE, Lancet JE, Kaufmann SH, End DW, Wright JJ, Bol K, et al. Clinical and Biological Activity of the Farnesyltransferase Inhibitor R115777 in Adults with Refractory and Relapsed Acute Leukemias: A Phase I Clinical-Laboratory Correlative Trial. Blood. 2001;97(11):3361-3369.
39. Copp J, Manning G, Hunter T. TORC-spe-cific phosphorylation of mammalian target of rapamycin (mTOR): phospho-Ser2481 is a marker for intact mTOR signaling complex 2. Cancer Res. 2009;69(5):1821-1827.
40. Carboni JM, Yan N, Cox AD, Bustelo X, Graham SM, Lynch MJ, et al. Farnesyltransferase inhibitors are inhibitors of Ras but not R-Ras2/TC21, transformation. Oncogene. 1995;10(10):1905-1913.
41. Prendergast GC, Rane N. Farnesyltransferase inhibitors: mechanism and applications. Expert Opin Investig Drugs. 2001;10(12): 2105-2116.
42. Berndt N, Hamilton AD, Sebti SM. Targeting protein prenylation for cancer therapy. Nat Rev Cancer. 2011;11(11):775-791.
43. Sebti SM, Der CJ. Opinion: Searching for the elusive targets of farnesyltransferase inhibitors. Nat Rev Cancer. 2003;3(12):945-951.
44. Beaupre DM, Cepero E, Obeng EA, Boise LH, Lichtenheld MG. R115777 induces Ras-independent apoptosis of myeloma cells via multiple intrinsic pathways. Mol Ca Therap. 2004;3(2):179-186.
45. Ren D, Tu HC, Kim H, Wang GX, Bean GR, Takeuchi O, et al. BID, BIM, and PUMA are essential for activation of the BAX- and BAK-dependent cell death program. Science. 2010;330(6009):1390-1393.
46. Schimmer AD, Pedersen IM, Kitada S, Eksioglu-Demiralp E, Minden MD, Pinto R, et al. Functional blocks in caspase activation pathways are common in leukemia and predict patient response to induction chemotherapy. Cancer Res. 2003;63(6): 1242-1248.
47. Dower NA, Stang SL, Bottoroff DA, Ebinu JO, Dickie P, Ostergaaard HL, et al. RasGRP is essential for mouse thymocyte differentiation and TCR signaling. Nature Immunol. 2000;1(4):317-321.
48. Coughlin JJ, Stang SL, Dower NA, Stone JC. RasGRP1 and RasGRP3 regulate B cell proliferation by facilitating B cell receptor-Ras signaling. J Immunol. 2005;175(11):7179-7184.
49. Lee SH, Yun S, Lee J, Kim MJ, Piao ZH, Jeong M, et al. RasGRP1 is required for human NK cell function. Journal of Immunology. 2009;183(12):7931-8.
50. Tognon CE, Kirk HE, Passmore LA, Whitehead I P, Der CJ, Kay RJ. Regulation of RasGRP via a phorbol ester-responsive C1 domain. Mol Cell Biol. 1998;18(12):6995-7008.