Targeting of polo-like kinases and their cross talk with Aurora kinases possible therapeutic strategies in human acute myeloid leukemia?

Expert Opinion on Investigational Drugs

Volumn 21, Issue 5, 2012, Pages 587-603

  Tsykunova, Galina ^a   Reikvam, Håkon ^a,b   Ahmed, Aymen Bushra ^a   Nepstad, Ina ^b   Gjertsen, Bjørn Tore ^a,b   Bruserud, Øystein ^a,b  

^a HAUKELAND UNIVERSITY HOSPITAL   (Norway)

^b UNIVERSITY OF BERGEN   (Norway)

Author keywords

Acute myeloid leukemia; Aurora kinase; Chemotherapy; Clinical trials; Polo like kinase

Indexed keywords

1 CYCLOPROPYL 3 [3 (5 MORPHOLINOMETHYL 1H BENZIMIDAZOL 2 YL) 1H PYRAZOL 4 YL]UREA; 4 (8 CYCLOPENTYL 7 ETHYL 5,6,7,8 TETRAHYDRO 5 METHYL 6 OXO 2 PTERIDINYLAMINO) 3 METHOXY N (1 METHYL 4 PIPERIDINYL)BENZAMIDE; 4 [[9 CHLORO 7 (2,6 DIFLUOROPHENYL) 5H PYRIMIDO[5,4 D][2]BENZAZEPIN 2 YL]AMINO]BENZOIC ACID; ALISERTIB; AS 03569; AURORA A KINASE; AURORA KINASE INHIBITOR; BARASERTIB; CENISERTIB; CYC 116; DANUSERTIB; ENMD 2076; GSK 1070916A; GSK 461364; HMN 214; NMS 1286937; ONO 1910NA; POLO LIKE KINASE; POLO LIKE KINASE 1; POLO LIKE KINASE 2; POLO LIKE KINASE 3; POLO LIKE KINASE 4; POLO LIKE KINASE INHIBITOR; SNS 314; TOZASERTIB; UNCLASSIFIED DRUG; VOLASERTIB;

ABDOMINAL PAIN; ACUTE GRANULOCYTIC LEUKEMIA; ALKALINE PHOSPHATASE BLOOD LEVEL; ALLERGIC REACTION; ALOPECIA; AMINOTRANSFERASE BLOOD LEVEL; ANEMIA; ANOREXIA; ANTINEOPLASTIC ACTIVITY; ARTHRALGIA; BONE PAIN; CANCER PAIN; CLINICAL TRIAL (TOPIC); CONFUSION; CONSTIPATION; COORDINATION DISORDER; CYSTITIS; DECREASED APPETITE; DEHYDRATION; DIARRHEA; DIZZINESS; DRUG TARGETING; DYSPNEA; EDEMA; ENZYME ANALYSIS; ENZYME INHIBITION; EPISTAXIS; FATIGUE; FEBRILE NEUTROPENIA; FEVER; FLATULENCE; GASTROINTESTINAL SYMPTOM; GLOSSODYNIA; HEADACHE; HEART INFARCTION; HEART LEFT VENTRICLE EJECTION FRACTION; HERPES ZOSTER; HUMAN; HYPERBILIRUBINEMIA; HYPERGLYCEMIA; HYPERSENSITIVITY REACTION; HYPERTENSION; HYPERTRANSAMINASEMIA; HYPONATREMIA; HYPOPHOSPHATEMIA; INFECTION; JAUNDICE; LEUKEMOGENESIS; LEUKOPENIA; LUNG EMBOLISM; LYMPHOCYTOPENIA; MOTOR NEUROPATHY; MUCOSA INFLAMMATION; MUSCLE WEAKNESS; MYALGIA; NAUSEA; NEUTROPENIA; PAIN; PELVIS PAIN SYNDROME; PERIPHERAL EDEMA; PERIPHERAL NEUROPATHY; PLEURA EFFUSION; PNEUMONIA; RASH; REVIEW; RIGOR; SIDE EFFECT; SOMNOLENCE; STOMACH ULCER; STOMATITIS; THORAX PAIN; THROMBOCYTOPENIA; THROMBOEMBOLISM; URINARY TRACT INFECTION; VERTIGO; VOMITING;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL CYCLE PROTEINS; HUMANS; LEUKEMIA, MYELOID, ACUTE; PROTEIN KINASE INHIBITORS; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS;

EID: 84859704856     PISSN: 13543784     EISSN: 17447658     Source Type: Journal    
DOI: 10.1517/13543784.2012.668525     Document Type: Review

References (119)

1. Dohner K, Dohner H. Molecular characterization of acute myeloid leukemia. Haematologica 2008;93(7):976-82 (Pubitemid 351957013)
2. Sunkel CE, Glover DM. Polo, a mitotic mutant of Drosophila displaying abnormal spindle poles. J Cell Sci 1988;89(Pt 1):25-38
3. Barr FA, Sillje HH, Nigg EA. Polo-like kinases and the orchestration of cell division. Nat Rev Mol Cell Biol 2004;5(6):429-40. (Pubitemid 38745493)
4. Chopra P, Sethi G, Dastidar SG, Ray A. Polo-like kinase inhibitors: an emerging opportunity for cancer therapeutics. Expert Opin Investig Drugs 2010;19(1):27-43
5. Park JE, Soung NK, Johmura Y, et al. Polo-box domain: a versatile mediator of polo-like kinase function. Cell Mol Life Sci 2010;67(12):1957-70
6. Toyoshima-Morimoto F, Taniguchi E, Nishida E. Plk1 promotes nuclear translocation of human Cdc25C during prophase. EMBO Rep 2002;3(4):341-8 (Pubitemid 34467604)
7. Walsh S, Margolis SS, Kornbluth S. Phosphorylation of the cyclin b1 cytoplasmic retention sequence by mitogen-activated protein kinase and Plx. Mol Cancer Res 2003;1(4):280-9 (Pubitemid 36292613)
8. Hansen DV, Loktev AV, Ban KH, Jackson PK. Plk1 regulates activation of the anaphase promoting complex by phosphorylating and triggering SCFbetaTrCP-dependent destruction of the APC inhibitor emi1. Mol Biol Cell 2004;15(12):5623-34 (Pubitemid 39564753)
9. Takaki T, Trenz K, Costanzo V, Petronczki M. Polo-like kinase 1 reaches beyond mitosis-cytokinesis, DNA damage response, and development. Curr Opin Cell Biol 2008;20(6):650-60.
10. Takahashi T, Sano B, Nagata T, et al. Polo-like kinase 1 (PLK1) is overexpressed in primary colorectal cancers. Cancer Sci 2003;94(2):148-52 (Pubitemid 36575873)
11. Weichert W, Kristiansen G, Schmidt M, et al. Polo-like kinase 1 expression is a prognostic factor in human colon cancer. World J Gastroenterol 2005;11(36):5644-50 (Pubitemid 41684917)
12. Wolf G, Elez R, Doermer A, et al. Prognostic significance of polo-like kinase (PLK) expression in non-small cell lung cancer. Oncogene 1997;14(5):543-9 (Pubitemid 27090956)
13. Ikezoe T, Yang J, Nishioka C, et al. A novel treatment strategy targeting polo-like kinase 1 in hematological malignancies. Leukemia 2009;23(9):1564-76
14. Didier C, Cavelier C, Quaranta M, et al. Evaluation of polo-like Kinase 1 inhibition on the G2/M checkpoint in acute myelocytic leukaemia. Eur J Pharmacol 2008;591(1-3):102-5.
15. Strebhardt K. Multifaceted polo-like kinases: drug targets and antitargets for cancer therapy. Nat Rev Drug Discov 2010;9(8):643-60
16. Archambault V, Glover DM. Polo-like kinases: conservation and divergence in their functions and regulation. Nat Rev Mol Cell Biol 2009;10(4):265-75
17. Strebhardt K, Ullrich A. Targeting polo-like kinase 1 for cancer therapy. Nat Rev Cancer 2006;6(4):321-30
18. Strebhardt K. Small molecules keep mitotic kinases in check. ACS Chem Biol 2006;1(11):683-6
19. Jang YJ, Ma S, Terada Y, Erikson RL. Phosphorylation of threonine 210 and the role of serine 137 in the regulation of mammalian polo-like kinase. J Biol Chem 2002;277(46):44115-20 (Pubitemid 36157840)
20. Seki A, Coppinger JA, Jang CY, et al. Bora and the kinase aurora a cooperatively activate the kinase Plk1 and control mitotic entry. Science 2008;320(5883):1655-8. (Pubitemid 351931258)
21. Macurek L, Lindqvist A, Lim D, et al. Polo-like kinase-1 is activated by aurora A to promote checkpoint recovery. Nature 2008;455(7209):119-23.
22. Andrysik Z, Bernstein WZ, Deng L, et al. The novel mouse polo-like kinase 5 responds to DNA damage and localizes in the nucleolus. Nucleic Acids Res 2010;38(9):2931-43
23. Jackman M, Lindon C, Nigg EA, Pines J. Active cyclin B1-Cdk1 first appears on centrosomes in prophase. Nat Cell Biol 2003;5(2):143-8 (Pubitemid 36204196)
24. Yuan J, Eckerdt F, Bereiter-Hahn J, et al. Cooperative phosphorylation including the activity of polo-like kinase 1 regulates the subcellular localization of cyclin B1. Oncogene 2002;21(54):8282-92 (Pubitemid 35477868)
25. Winkles JA, Alberts GF. Differential regulation of polo-like kinase 1, 2, 3, and 4 gene expression in mammalian cells and tissues. Oncogene 2005;24(2):260-6 (Pubitemid 40188606)
26. Holtrich U, Wolf G, Brauninger A, et al. Induction and down-regulation of PLK, a human serine/threonine kinase expressed in proliferating cells and tumors. Proc Natl Acad Sci USA 1994;91(5):1736-40 (Pubitemid 24080280)
27. Warnke S, Kemmler S, Hames RS, et al. Polo-like kinase-2 is required for centriole duplication in mammalian cells. Curr Biol 2004;14(13):1200-7 (Pubitemid 38893984)
28. Wang Q, Xie S, Chen J, et al. Cell cycle arrest and apoptosis induced by human polo-like kinase 3 is mediated through perturbation of microtubule integrity. Mol Cell Biol 2002;22(10):3450-9 (Pubitemid 34453984)
29. Zimmerman WC, Erikson RL. Finding Plk3. Cell Cycle 2007;6(11):1314-18 (Pubitemid 47327963)
30. Holtrich U, Wolf G, Yuan J, et al. Adhesion induced expression of the serine/threonine kinase Fnk in human macrophages. Oncogene 2000;19(42):4832-9
31. van Vugt MA, Medema RH. Getting in and out of mitosis with polo-like kinase-1. Oncogene 2005;24(17):2844-59 (Pubitemid 40638094)
32. Habedanck R, Stierhof YD, Wilkinson CJ, Nigg EA. The polo kinase Plk4 functions in centriole duplication. Nat Cell Biol 2005;7(11):1140-6
33. de Carcer G, Manning G, Malumbres M. From Plk1 to Plk5: functional evolution of polo-like kinases. Cell Cycle 2011;10(14):2255-62
34. de Carcer G, Escobar B, Higuero AM, et al. Plk5, a polo box domain-only protein with specific roles in neuron differentiation and glioblastoma suppression. Mol Cell Biol 2011;31(6):1225-39
35. Raab M, Kappel S, Kramer A, et al. Toxicity modelling of Plk1-targeted therapies in genetically engineered mice and cultured primary mammalian cells. Nat Commun 2011;2:395
36. Ma S, Charron J, Erikson RL. Role of Plk2 (Snk) in mouse development and cell proliferation. Mol Cell Biol 2003;23(19):6936-43 (Pubitemid 37214661)
37. Yuan J, Horlin A, Hock B, et al. Polo-like kinase, a novel marker for cellular proliferation. Am J Pathol 1997;150(4):1165-72 (Pubitemid 27152634)
38. Yang Y, Bai J, Shen R, et al. Polo-like kinase 3 functions as a tumor suppressor and is a negative regulator of hypoxia-inducible factor-1 alpha under hypoxic conditions. Cancer Res 2008;68(11):4077-85
39. Lens SM, Voest EE, Medema RH. Shared and separate functions of polo-like kinases and aurora kinases in cancer. Nat Rev Cancer 2010;10(12):825-41
40. Benetatos L, Dasoula A, Hatzimichael E, et al. Polo-like kinase 2 (SNK/PLK2) is a novel epigenetically regulated gene in acute myeloid leukemia and myelodysplastic syndromes: genetic and epigenetic interactions. Ann Hematol 2011;90(9):1037-45
41. Li Z, Lu J, Sun M, et al. Distinct microRNA expression profiles in acute myeloid leukemia with common translocations. Proc Natl Acad Sci USA 2008;105(40):15535-40
42. Ramirez-Herrick AM, Mullican SE, Sheehan AM, Conneely OM. Reduced NR4A gene dosage leads to mixed myelodysplastic/myeloproliferative neoplasms in mice. Blood 2011;117(9):2681-90
43. Renner AG, Creancier L, Dos Santos C, et al. A functional link between polo-like kinase 1 and the mammalian target-of-rapamycin pathway? Cell Cycle 2010;9(9):1690-6
44. Renner AG, Dos Santos C, Recher C, et al. Polo-like kinase 1 is overexpressed in acute myeloid leukemia and its inhibition preferentially targets the proliferation of leukemic cells. Blood 2009;114(3):659-62
45. Yoshida S, Furukawa N, Haruta S, et al. Theoretical model of treatment strategies for clear cell carcinoma of the ovary: focus on perspectives. Cancer Treat Rev 2009;35(7):608-15
46. Moshe Y, Boulaire J, Pagano M, Hershko A. Role of Polo-like kinase in the degradation of early mitotic inhibitor 1, a regulator of the anaphase promoting complex/cyclosome. Proc Natl Acad Sci USA 2004;101(21):7937-42 (Pubitemid 38698032)
47. Toyoshima-Morimoto F, Taniguchi E, Shinya N, et al. Polo-like kinase 1 phosphorylates cyclin B1 and targets it to the nucleus during prophase. Nature 2001;410(6825):215-20 (Pubitemid 32216594)
48. Ersvaer E, Zhang JY, McCormack E, et al. Cyclin B1 is commonly expressed in the cytoplasm of primary human acute myelogenous leukemia cells and serves as a leukemia-associated antigen associated with autoantibody response in a subset of patients. Eur J Haematol 2007;79(3):210-25 (Pubitemid 47231163)
49. Macurek L, Lindqvist A, Medema RH. Aurora-a and hBora join the game of polo. Cancer Res 2009;69(11):4555-8
50. Moore AS, Blagg J, Linardopoulos S, Pearson AD. Aurora kinase inhibitors: novel small molecules with promising activity in acute myeloid and Philadelphia-positive leukemias. Leukemia 2010;24(4):671-8
51. Lapenna S, Giordano A. Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov 2009;8(7):547-66
52. Cheong JW, Jung HI, Eom JI, et al. Aurora-a kinase inhibition enhances the cytosine arabinoside-induced cell death in leukemia cells through apoptosis and mitotic catastrophe. Cancer Lett 2010;297(2):171-81
53. D'Alise AM, Amabile G, Iovino M, et al. Reversine, a novel Aurora kinases inhibitor, inhibits colony formation of human acute myeloid leukemia cells. Mol Cancer Ther 2008;7(5):1140-9
54. Grundy M, Seedhouse C, Shang S, et al. The FLT3 internal tandem duplication mutation is a secondary target of the aurora B kinase inhibitor AZD1152-HQPA in acute myelogenous leukemia cells. Mol Cancer Ther 2010;9(3):661-72
55. Huang XF, Luo SK, Xu J, et al. Aurora kinase inhibitory VX-680 increases Bax/Bcl-2 ratio and induces apoptosis in aurora-a-high acute myeloid leukemia. Blood 2008;111(5):2854-65
56. Yang J, Ikezoe T, Nishioka C, et al. AZD1152, a novel and selective aurora B kinase inhibitor, induces growth arrest, apoptosis, and sensitization for tubulin depolymerizing agent or topoisomerase II inhibitor in human acute leukemia cells in vitro and in vivo. Blood 2007;110(6):2034-40 (Pubitemid 47443920)
57. Ye D, Garcia-Manero G, Kantarjian HM, et al. Analysis of aurora kinase a expression in CD34(+) blast cells isolated from patients with myelodysplastic syndromes and acute myeloid leukemia. J Hematop 2009;2(1):2-8
58. Bug G, Muller-Tidow C, Schlenk RF, et al. Phase I/II study of BU 6727 (volasertib), an intravenous Polo-Like Kinase-1 (PLK) inhibitor, in patients with acute myeloid leukemia (AML): results of the dose finding for BI 6727 in combination with a low-dose Cytarabine. 53rd ASH annual meeting, poster, 2010; 2011
59. Stadler WM, Vaughn DJ, Sonpavde G, et al. Phase II study of single-agent volasertib (BI 6727) for second-line treatment of urothelial cancer (UC). Presented in genitourinary cancer symposium, 2011, general poster section; 2011
60. Garland LL, Taylor C, Pilkington DL, et al. A phase I pharmacokinetic study of HMN-214, a novel oral stilbene derivative with polo-like kinase-1-interacting properties, in patients with advanced solid tumors. Clin Cancer Res 2006;12(17):5182-9 (Pubitemid 44453347)
61. Hofheinz RD, Al-Batran SE, Hochhaus A, et al. An open-label, phase I study of the polo-like kinase-1 inhibitor, BI 2536, in patients with advanced solid tumors. Clin Cancer Res 2010;Sep1516(18):4666-74
62. Jimeno A, Li J, Messersmith WA, et al. Phase I study of ON 01910.Na, a novel modulator of the Polo-like kinase 1 pathway, in adult patients with solid tumors. J Clin Oncol 2008;26(34):5504-10
63. Mross K, Frost A, Steinbild S, et al. Phase I dose escalation and pharmacokinetic study of BI 2536, a novel Polo-like kinase 1 inhibitor, in patients with advanced solid tumors. J Clin Oncol 2008;26(34):5511-17
64. Mross K, DC, Aulitszky WE, et al. A randomized fase II trial of the novel polo-like kinase inhibitor BI2536 in cheminaive patients with unresectable pancreatic cancer-a study in cooperation with the CESAR network of investigator. Presentet at the 33rd Annual Congress of the European Society of Medical Oncology; 12-16 September 2008; Stockholm, Sweden; 2008
65. Olmos D, Barker D, Sharma R, et al. Phase I study of GSK461364, a specific and competitive Polo-like kinase 1 inhibitor, in patients with advanced solid malignancies. Clin Cancer Res 2011;17(10):3420-30
66. Pandha HS, Protheroe A, Wylie J, et al. An open label phase II trial of BI2536, a novel Plk 1 inhibitor, in patients with metastatic hormone refractory prostate cancer (HRPC). J Clin Oncol 2008;26:(abstract)14547
67. Rudolph D, Steegmaier M, Hoffmann M, et al. B6727, a polo-like kinase inhibitor with improved pharmacokinetic profile and broad antitumor activity. Clin Cancer Res 2009;15(9):3094-102
68. Schoffski P, Awada A, Dumez H, et al. A phase I, dose-escalation study of the novel Polo-like kinase inhibitor volasertib (BI 6727) in patients with advanced solid tumours. Eur J Cancer 2012;48(2):179-86
69. Schoffski P, Blay JY, De Greve J, et al. Multicentric parallel phase II trial of the polo-like kinase 1 inhibitor BI 2536 in patients with advanced head and neck cancer, breast cancer, ovarian cancer, soft tissue sarcoma and melanoma. The first protocol of the European Organization for Research and Treatment of Cancer (EORTC) Network Of Core Institutes (NOCI). Eur J Cancer 2010;46(12):2206-15
70. Sebastian M, Reck M, Waller CF, et al. The efficacy and safety of BI 2536, a novel Plk-1 inhibitor, in patients with stage IIIB/IV non-small cell lung cancer who had relapsed after, or failed, chemotherapy: results from an open-label, randomized phase II clinical trial. J Thorac Oncol 2010;5(7):1060-7
71. Takai N, Ueda T, Nasu K, Narahara H. Erucylphosphocholine shows a strong anti-growth activity in human endometrial and ovarian cancer cells. Gynecol Oncol 2008;111(2):336-43
72. Jiang PD, Zhao YL, Shi W, et al. Cell growth inhibition, G2/M cell cycle arrest, and apoptosis induced by chloroquine in human breast cancer cell line Bcap-37. Cell Physiol Biochem 2008;22(5-6):431-40
73. Liu Y, Jiang N, Wu J, et al. Polo-like kinases inhibited by wortmannin. Labeling site and downstream effects. J Biol Chem 2007;282(4):2505-11 (Pubitemid 47076790)
74. Schoffski P. Polo-like kinase (PLK) inhibitors in preclinical and early clinical development in oncology. Oncologist 2009;14(6):559-70
75. Boss DS, Witteveen PO, van der Sar J, et al. Clinical evaluation of AZD1152, an i.v. inhibitor of Aurora B kinase, in patients with solid malignant tumors. Ann Oncol 2011;22(2):431-7
76. Cohen RB, Jones SF, Aggarwal C, et al. A phase I dose-escalation study of danusertib (PHA-739358) administered as a 24-hour infusion with and without granulocyte colony-stimulating factor in a 14-day cycle in patients with advanced solid tumors. Clin Cancer Res 2009;15(21):6694-701
77. Dees EC, Infante JR, Cohen RB, et al. Phase 1 study of MLN8054, a selective inhibitor of Aurora A kinase in patients with advanced solid tumors. Cancer Chemother Pharmacol 2011;67(4):945-54
78. Diamond JR, Bastos BR, Hansen RJ, et al. Phase I safety, pharmacokinetic, and pharmacodynamic study of ENMD-2076, a novel angiogenic and aurora kinase inhibitor, in patients with advanced solid tumors. Clin Cancer Res 2011;17(4):849-60
79. Robert F, Verschraegen C, Hurwitz H, et al. A phase I trial of SNS-314, a novel selective pan-aurora kinase, inhibitor, in advanced solid tumor patients general poster session, developmental therapeutics: cytotoxic therapy. J Clin Oncol 2009;27(15s suppl):abstract 2536
80. Renshaw JS, Patnaik A, Gordon M, et al. A phase 1 two arm trial of AS703569, an orally available aurora kinase inhibitor, in subjects with solid tumors: preliminary results. J Clin Oncol 2007;25(Suppl):abstract 14130
81. Macarulla T, Cervantes A, Elez E, et al. Phase I study of the selective Aurora A kinase inhibitor MLN8054 in patients with advanced solid tumors: safety, pharmacokinetics, and pharmacodynamics. Mol Cancer Ther 2010;9(10):2844-52
82. Kristeleit R, HC, Arkenau H, et al. A phase I study of AT9283, an aurora kinase inhibitor, in patients with refractory solid tumors. 2009 ASCO annual meeting, genetal poster session. J Clin Oncol 2009;27(15s suppl):abstract 2566
83. Traynor AM, Hewitt M, Liu G, et al. Phase I dose escalation study of MK-0457, a novel Aurora kinase inhibitor, in adult patients with advanced solid tumors. Cancer Chemother Pharmacol 2011;67(2):305-14
84. Chun AW, Cosenza SC, Taft DR, Maniar M. Preclinical pharmacokinetics and in vitro activity of ON 01910.Na, a novel anti-cancer agent. Cancer Chemother Pharmacol 2009;65(1):177-86
85. Medina-Gundrum L, Cerna C, Gomez L, Izbicka E. Investigation of HMN-176 anticancer activity in human tumor specimens in vitro and the effects of HMN-176 on differential gene expression. Invest New Drugs 2005;23(1):3-9 (Pubitemid 39505947)
86. Fredly H, Ersvaer E, Camilla S, et al. The combination of conventional chemotherapy with new targeted therapy in hematologic malignancies: the safety and efficiency of Low-Dose Cytarabine supports its combination with new therapeutic agents in early clinical trials. Curr Cancer Ther Rev 2009;5:243-55; 13
87. Parker WB, Shaddix SC, Chang CH, et al. Effects of 2-chloro-9-(2-deoxy-2- fluoro-beta-D-arabinofuranosyl)adenine on K562 cellular metabolism and the inhibition of human ribonucleotide reductase and DNA polymerases by its 5'-triphosphate. Cancer Res 1991;51(9):2386-94
88. Genini D, Adachi S, Chao Q, et al. Deoxyadenosine analogs induce programmed cell death in chronic lymphocytic leukemia cells by damaging the DNA and by directly affecting the mitochondria. Blood 2000;96(10):3537-43
89. Parker WB, Allan PW, Hassan AE, et al. Antitumor activity of 2-fluoro-2'-deoxyadenosine against tumors that express Escherichia coli purine nucleoside phosphorylase. Cancer Gene Ther 2003;10(1):23-9 (Pubitemid 36222073)
90. Carson DA, Wasson DB, Esparza LM, et al. Oral antilymphocyte activity and induction of apoptosis by 2-chloro-2'-arabino-fluoro-2'-deoxyadenosine. Proc Natl Acad Sci USA 1992;89(7):2970-4
91. Xie C, Plunkett W. Metabolism and actions of 2-chloro-9-(2-deoxy-2- fluorobeta-D-arabinofuranosyl)-adenine in human lymphoblastoid cells. Cancer Res 1995;55(13):2847-52
92. Kline JP, Larson RA. Clofarabine in the treatment of acute myeloid leukaemia and acute lymphoblastic leukaemia: a review. Expert Opin Pharmacother 2005;6(15):2711-18. (Pubitemid 41824385)
93. Faderl S, Gandhi V, O'Brien S, et al. Results of a phase 1-2 study of clofarabine in combination with cytarabine (ara-C) in relapsed and refractory acute leukemias. Blood 2005;105(3):940-7 (Pubitemid 40170859)
94. Schiffer CA. Acute myeloid leukemia in adults: where do we go from here? Cancer Chemother Pharmacol 2001;48(Suppl 1):S45-52
95. Cooper T, Ayres M, Nowak B, Gandhi V. Biochemical modulation of cytarabine triphosphate by clofarabine. Cancer Chemother Pharmacol 2005;55(4):361-8 (Pubitemid 40379260)
96. Spasokoukotskaja T, Sasvari-Szekely M, Keszler G, et al. Treatment of normal and malignant cells with nucleoside analogues and etoposide enhances deoxycytidine kinase activity. Eur J Cancer 1999;35(13):1862-7 (Pubitemid 29512320)
97. Kantarjian HM, Gandhi V, Kozuch P, et al. Phase I clinical and pharmacology study of clofarabine in patients with solid and hematologic cancers. J Clin Oncol 2003;21(6):1167-73 (Pubitemid 46594149)
98. Becker PS, Kantarjian HM, Appelbaum FR, et al. Clofarabine with high dose cytarabine and granulocyte colony-stimulating factor (G-CSF) priming for relapsed and refractory acute myeloid leukaemia. Br J Haematol 2011;155(2):182-9
99. Agura E, Cooper B, Holmes H, et al. Report of a phase II study of clofarabine and cytarabine in de novo and relapsed and refractory AML patients and in selected elderly patients at high risk for anthracycline toxicity. Oncologist 2011;16(2):197-206
100. Farag SS, Wood LL, Schwartz JE, et al. Phase I trial and pharmacokinetic study of high-dose clofarabine and busulfan and allogeneic stem cell transplantation in adults with high-risk and refractory acute leukemia. Leukemia 2011;25(4):599-605
101. Andersson BS, Valdez BC, de Lima M, et al. Clofarabine +-fludarabine with once daily i.v. busulfan as pretransplant conditioning therapy for advanced myeloid leukemia and MDS. Biol Blood Marrow Transplant 2011;17(6):893-900
102. Burnett AK, Russell NH, Kell J, et al. European development of clofarabine as treatment for older patients with acute myeloid leukemia considered unsuitable for intensive chemotherapy. J Clin Oncol 2010;28(14):2389-95
103. Kantarjian HM, Erba HP, Claxton D, et al. Phase II study of clofarabine monotherapy in previously untreated older adults with acute myeloid leukemia and unfavorable prognostic factors. J Clin Oncol 2010;28(4):549-55
104. Faderl S, Ravandi F, Huang X, et al. A randomized study of clofarabine versus clofarabine plus low-dose cytarabine as front-line therapy for patients aged 60 years and older with acute myeloid leukemia and high-risk myelodysplastic syndrome. Blood 2008;112(5):1638-45
105. Bruserud O, Stapnes C, Ersvaer E, et al. Histone deacetylase inhibitors in cancer treatment: a review of the clinical toxicity and the modulation of gene expression in cancer cell. Curr Pharm Biotechnol 2007;8(6):388-400 (Pubitemid 350268198)
106. Bruserud O, Stapnes C, Tronstad KJ, et al. Protein lysine acetylation in normal and leukaemic haematopoiesis: HDACs as possible therapeutic targets in adult AML. Expert Opin Ther Targets 2006;10(1):51-68 (Pubitemid 43263266)
107. Saban N, Bujak M. Hydroxyurea and hydroxamic acid derivatives as antitumor drugs. Cancer Chemother Pharmacol 2009;64(2):213-21
108. Burnett AK, Milligan D, Prentice AG, et al. A comparison of low-dose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not considered fit for intensive treatment. Cancer 2007;109(6):1114-24 (Pubitemid 46435390)
109. Petti MC, Tafuri A, Latagliata R, et al. High-dose hydroxyurea in the treatment of poor-risk myeloid leukemias. Ann Hematol 2003;82(8):476-80 (Pubitemid 37062745)
110. Mori M, Ohta M, Miyata A, et al. Treatment of acute myeloid leukemia patients aged more than 75 years: results of the E-AML-01 trial of the Japanese Elderly Leukemia and Lymphoma Study Group (JELLSG). Leuk Lymphoma 2006;47(10):2062-9 (Pubitemid 44650081)
111. Miyawaki S, Sakamaki H, Ohtake S, et al. A randomized, postremission comparison of four courses of standard-dose consolidation therapy without maintenance therapy versus three courses of standard-dose consolidation with maintenance therapy in adults with acute myeloid leukemia: the Japan Adult Leukemia Study Group AML 97 Study. Cancer 2005;104(12):2726-34 (Pubitemid 41799616)
112. 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 LeukemiaNet. Blood 2010;115(3):453-74
113. Ryningen A, Stapnes C, Lassalle P, et al. A subset of patients with high-risk acute myelogenous leukemia shows improved peripheral blood cell counts when treated with the combination of valproic acid, theophylline and all-trans retinoic acid. Leuk Res 2009;33(6):779-87
114. Huang X, Ruan Q, Fang Y, et al. Physical and functional interactions between mitotic kinases during polyploidization and megakaryocytic differentiation. Cell cycle 2004;3(7):946-51 (Pubitemid 40179477)
115. Yagi M, Roth GJ. Megakaryocyte polyploidization is associated with decreased expression of polo-like kinase (PLK). J Thromb Haemost 2006;4(9):2028-34 (Pubitemid 44226785)
116. Zhang Y, Nagata Y, Yu G, et al. Aberrant quantity and localization of Aurora-B/AIM-1 and survivin during megakaryocyte polyploidization and the consequences of Aurora-B/AIM-1-deregulated expression. Blood 2004;103(10):3717-26 (Pubitemid 38596287)
117. Lordier L, Chang Y, Jalil A, et al. Aurora B is dispensable for megakaryocyte polyploidization, but contributes to the endomitotic process. Blood 2010;116(13):2345-55
118. Lowenberg B, Muus P, Ossenkoppele G, et al. Phase I/II study to assess the safety, efficacy and pharmacokinetics of barasertib (AZD1152) in patients with advanced acute myeloid leukemia. Blood 2011 [Epub ahead of print]
119. Hagop M, Kantarjian M, Mikkael A, et al. Phase I study to assess the safety and tolerability of AZD1152 in combination with low dose cytosine akabinoside in patients with acute myeloid leukemia (AML). Blood 2011;116(21):(abstract)656