Novel therapies for children with acute myeloid leukaemia

Leukemia

Volumn 27, Issue 7, 2013, Pages 1451-1460

  Moore, A S ^a,b,c   Kearns, P R ^d,e   Knapper, S ^f   Pearson, A D J ^c,e   Zwaan, C M ^e,g  

^a ROYAL CHILDREN'S HOSPITAL   (Australia)

^b LADY CILENTO CHILDREN S HOSPITAL   (Australia)

^c INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^d UNIVERSITY OF BIRMINGHAM   (United Kingdom)

^e European Consortium ^*  (United Kingdom)

^f CARDIFF UNIVERSITY   (United Kingdom)

^g SOPHIA CHILDREN S HOSPITAL   (Netherlands)

Author keywords

Acute myeloid leukaemia; AML; Chemotherapy; Children; Inhibitors; Novel therapeutics

Indexed keywords

1 CYCLOPROPYL 3 [3 (5 MORPHOLINOMETHYL 1H BENZIMIDAZOL 2 YL) 1H PYRAZOL 4 YL]UREA; 5 AZA 2' DEOXYCYTIDINE; 8 [4 (1 AMINOCYCLOBUTYL)PHENYL] 9 PHENYL 1,2,4 TRIAZOLO[3,4 F][1,6]NAPHTHYRIDIN 3(2H) ONE; ALISERTIB; BORTEZOMIB; BRENTUXIMAB VEDOTIN; CALICHEAMICIN; CLOFARABINE; CYTARABINE; DAUNORUBICIN; DOXORUBICIN; ETOPOSIDE; FENRETINIDE; GEMTUZUMAB OZOGAMICIN; LESTAURTINIB; MIDOSTAURIN; MITOXANTRONE; NAVELBINE; OBATOCLAX; PANABINOSTAT; PLACEBO; PROTEASOME INHIBITOR; QUIZARTINIB; RAZOXANE; RUXOLITINIB; SORAFENIB; THIOTEPA; TOPOTECAN; UNCLASSIFIED DRUG; UNINDEXED DRUG; VINCRISTINE;

ACUTE GRANULOCYTIC LEUKEMIA; ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION; AMINOTRANSFERASE BLOOD LEVEL; BONE MARROW SUPPRESSION; CANCER COMBINATION CHEMOTHERAPY; CANCER IMMUNOTHERAPY; CANCER INCIDENCE; CANCER PATIENT; CATHETER INFECTION; CHILD; CHILDHOOD CANCER; CLINICAL TRIAL (TOPIC); DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; EPISTAXIS; FEBRILE NEUTROPENIA; FEVER; HEALTH CARE QUALITY; HUMAN; HYPOKALEMIA; HYPOTENSION; IC 50; IN VITRO STUDY; IN VIVO STUDY; INTERNATIONAL COOPERATION; LEUKEMIA REMISSION; LIVER TOXICITY; MULTIPLE CYCLE TREATMENT; NAUSEA; OVERALL SURVIVAL; PHARMACODYNAMICS; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; REVIEW; SIDE EFFECT; SINGLE DRUG DOSE; SKIN TOXICITY;

ADENINE NUCLEOTIDES; AMINOGLYCOSIDES; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTINEOPLASTIC AGENTS; ARABINONUCLEOSIDES; CHILD; HUMANS; IMMUNOTOXINS; LEUKEMIA, MONOCYTIC, ACUTE; NIACINAMIDE; PHENYLUREA COMPOUNDS; PROTEIN KINASE INHIBITORS;

EID: 84880289614     PISSN: 08876924     EISSN: 14765551     Source Type: Journal    
DOI: 10.1038/leu.2013.106     Document Type: Review

References (125)

1. Dores GM, Devesa SS, Curtis RE, Linet MS, Morton LM. Acute leukemia incidence and patient survival among children and adults in the United States, 2001-2007. Blood 2012; 119: 34-43.
2. Burnett A, Wetzler M, Lowenberg B. Therapeutic advances in acute myeloid leukemia. J Clin Oncol 2011; 29: 487-494.
3. Gibson BE, Webb DK, Howman AJ, De Graaf SS, Harrison CJ, Wheatley K. Results of a randomized trial in children with Acute Myeloid Leukaemia: Medical Research Council AML12 trial. Br J Haematol 2011; 155: 366-376.
4. Pui CH, Carroll WL, Meshinchi S, Arceci RJ. Biology, Risk Stratification, and Therapy of Pediatric Acute Leukemias: An Update. J Clin Oncol 2011; 29: 551-565.
5. Creutzig U, van den Heuvel-Eibrink MM, Gibson B, Dworzak MN, Adachi S, de Bont E et al. Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel, on behalf of the AML Committee of the International BFM Study Group. Blood 2012; 120: 3187-3205.
6. Rubnitz JE, Gibson B, Smith FO. Acute myeloid leukemia. Pediatr Clin North Am 2008; 55: 21-51ix.
7. Stevens RF, Hann IM, Wheatley K, Gray RG. Marked improvements in outcome with chemotherapy alone in paediatric acute myeloid leukemia: results of the United Kingdom Medical Research Council's 10th AML trial. MRC Childhood Leukaemia Working Party. Br J Haematol 1998; 101: 130-140.
8. Kaspers GJ, Zimmermann M, Reinhardt D, Gibson BE, Tamminga RY, Aleinikova O et al. Improved outcome in pediatric relapsed acute myeloid leukemia: results of a randomized trial on liposomal daunorubicin by the International BFM Study Group. J Clin Oncol 2013; 31: 599-607.
9. Gorman MF, Ji L, Ko RH, Barnette P, Bostrom B, Hutchinson R et al. Outcome for children treated for relapsed or refractory acute myelogenous leukemia (rAML): a Therapeutic Advances in Childhood Leukemia (TACL) Consortium study. Pediatr Blood Cancer 2010; 55: 421-429.
10. Meadows AT, Friedman DL, Neglia JP, Mertens AC, Donaldson SS, Stovall M et al. Second neoplasms in survivors of childhood cancer: findings from the Childhood Cancer Survivor Study cohort. J Clin Oncol 2009; 27: 2356-2362.
11. Mulrooney DA, Yeazel MW, Kawashima T, Mertens AC, Mitby P, Stovall M et al. Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort. BMJ 2009; 339: b4606.
12. Ho PA, Alonzo TA, Kopecky KJ, Miller KL, Kuhn J, Zeng R et al. Molecular alterations of the IDH1 gene in AML: a Children's Oncology Group and Southwest Oncology Group study. Leukemia 2010; 24: 909-913.
13. Ho PA, Kutny MA, Alonzo TA, Gerbing RB, Joaquin J, Raimondi SC et al. Leukemic mutations in the methylation-associated genes DNMT3A and IDH2 are rare events in pediatric AML: a report from the Children's Oncology Group. Pediatr Blood Cancer 2011; 57: 204-209.
14. Damm F, Thol F, Hollink I, Zimmermann M, Reinhardt K, van den Heuvel-Eibrink MM et al. Prevalence and prognostic value of IDH1 and IDH2 mutations in childhood AML: a study of the AML-BFM and DCOG study groups. Leukemia 2011; 25: 1704-1710.
15. Langemeijer SM, Jansen JH, Hooijer J, van Hoogen P, Stevens-Linders E, Massop M et al. TET2 mutations in childhood leukemia. Leukemia 2011; 25: 189-192.
16. Juhl-Christensen C, Ommen HB, Aggerholm A, Lausen B, Kjeldsen E, Hasle H et al. Genetic and epigenetic similarities and differences between childhood and adult AML. Pediatr Blood Cancer 2012; 58: 525-531.
17. Pui CH, Jeha S, Kirkpatrick P. Clofarabine. Nat Rev Drug Discov 2005; 4: 369-370.
18. Rubnitz JE, Crews KR, Pounds S, Yang S, Campana D, Gandhi VV et al. Combination of cladribine and cytarabine is effective for childhood acute myeloid leukemia: results of the St Jude AML97 trial. Leukemia 2009; 23: 1410-1416.
19. Inaba H, Stewart CF, Crews KR, Yang S, Pounds S, Pui CH et al. Combination of cladribine plus topotecan for recurrent or refractory pediatric acute myeloid leukemia. Cancer 2010; 116: 98-105.
20. Chaleff S, Hurwitz CA, Chang M, Dahl G, Alonzo TA, Weinstein H. Phase II study of 2-chlorodeoxyadenosine plus idarubicin for children with acute myeloid leukaemia in first relapse: a paediatric oncology group study. Br J Haematol 2012; 156: 649-655.
21. Krance RA, Hurwitz CA, Head DR, Raimondi SC, Behm FG, Crews KR et al. Experience with 2-chlorodeoxyadenosine in previously untreated children with newly diagnosed acute myeloid leukemia and myelodysplastic diseases. J Clin Oncol 2001; 19: 2804-2811.
22. Abrahamsson J, Clausen N, Gustafsson G, Hovi L, Jonmundsson G, Zeller B et al. Improved outcome after relapse in children with acute myeloid leukaemia. Br J Haematol 2007; 136: 229-236.
23. Fleischhack G, Hasan C, Graf N, Mann G, Bode U. IDA-FLAG (idarubicin, fludarabine, cytarabine, G-CSF), an effective remission-induction therapy for poorprognosis AML of childhood prior to allogeneic or autologous bone marrow transplantation: experiences of a phase II trial. Br J Haematol 1998; 102: 647-655.
24. Bonate PL, Arthaud L, Cantrell Jr. WR, Stephenson K, Secrist 3rd JA, Weitman S. Discovery and development of clofarabine: a nucleoside analogue for treating cancer. Nat Rev Drug Discov 2006; 5: 855-863.
25. Jeha S, Razzouk B, Rytting M, Rheingold S, Albano E, Kadota R et al. Phase II study of clofarabine in pediatric patients with refractory or relapsed acute myeloid leukemia. J Clin Oncol 2009; 27: 4392-4397.
26. Johnston DL, Mandel KM. Fatal skin and liver toxicity in a patient treated with clofarabine. Pediatr Blood Cancer 2008; 50: 1082.
27. Inaba H, Rubnitz JE, Coustan-Smith E, Li L, Furmanski BD, Mascara GP et al. Phase I pharmacokinetic and pharmacodynamic study of the multikinase inhibitor sorafenib in combination with clofarabine and cytarabine in pediatric relapsed/refractory leukemia. J Clin Oncol 2011; 29: 3293-3300.
28. Hijiya N, Gaynon P, Barry E, Silverman L, Thomson B, Chu R et al. A multi-center phase I study of clofarabine, etoposide and cyclophosphamide in combination in pediatric patients with refractory or relapsed acute leukemia. Leukemia 2009; 23: 2259-2264.
29. Kearns P, Graham NJ, Cummins M, Gibson B, Grainger JD, Keenan R et al. Phase I study of clofarabine and liposomal daunorubicin in childhood acute myeloid leukemia. J Clin Oncol 2011; 29(suppl); abstr 9521.
30. Meshinchi S, Appelbaum FR. Structural and functional alterations of FLT3 in acute myeloid leukemia. Clin Cancer Res 2009; 15: 4263-4269.
31. Meshinchi S, Alonzo TA, Stirewalt DL, Zwaan M, Zimmerman M, Reinhardt D et al. Clinical implications of FLT3 mutations in pediatric AML. Blood 2006; 108: 3654-3661.
32. Levis M, Small D. FLT3: ITDoes matter in leukemia. Leukemia 2003; 17: 1738-1752.
33. Knapper S. The clinical development of FLT3 inhibitors in acute myeloid leukemia. Expert Opin Investig Drugs 2011; 20: 1377-1395.
34. Whitman SP, Archer KJ, Feng L, Baldus C, Becknell B, Carlson BD et al. Absence of the wild-type allele predicts poor prognosis in adult de novo acute myeloid leukemia with normal cytogenetics and the internal tandem duplication of FLT3: a cancer and leukemia group B study. Cancer Res 2001; 61: 7233-7239.
35. Gale RE, Green C, Allen C, Mead AJ, Burnett AK, Hills RK et al. The impact of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia. Blood 2008; 111: 2776-2784.
36. Pratz KW, Sato T, Murphy KM, Stine A, Rajkhowa T, Levis M. FLT3-mutant allelic burden and clinical status are predictive of response to FLT3 inhibitors in AML. Blood 2010; 115: 1425-1432.
37. Heidel F, Solem FK, Breitenbuecher F, Lipka DB, Kasper S, Thiede MH et al. Clinical resistance to the kinase inhibitor PKC412 in acute myeloid leukemia by mutation of Asn-676 in the FLT3 tyrosine kinase domain. Blood 2006; 107: 293-300.
38. Man CH, Fung TK, Ho C, Han HH, Chow HC, Ma AC et al. Sorafenib treatment of FLT3-ITD(+) acute myeloid leukemia: favorable initial outcome and mechanisms of subsequent nonresponsiveness associated with the emergence of a D835 mutation. Blood 2012; 119: 5133-5143.
39. Smith CC, Wang Q, Chin CS, Salerno S, Damon LE, Levis MJ et al. Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia. Nature 2012; 485: 260-263.
40. Swords R, Freeman C, Giles F. Targeting the FMS-like tyrosine kinase 3 in acute myeloid leukemia. Leukemia 2012; 26: 2176-2185.
41. Smith BD, Levis M, Beran M, Giles F, Kantarjian H, Berg K et al. Single-agent CEP- 701, a novel FLT3 inhibitor, shows biologic and clinical activity in patients with relapsed or refractory acute myeloid leukemia. Blood 2004; 103: 3669-3676.
42. Levis M, Brown P, Smith BD, Stine A, Pham R, Stone R et al. Plasma inhibitory activity (PIA): a pharmacodynamic assay reveals insights into the basis for cytotoxic response to FLT3 inhibitors. Blood 2006; 108: 3477-3483.
43. Knapper S, Burnett AK, Littlewood T, Kell WJ, Agrawal S, Chopra R et al. A phase 2 trial of the FLT3 inhibitor lestaurtinib (CEP701) as first-line treatment for older patients with acute myeloid leukemia not considered fit for intensive chemotherapy. Blood 2006; 108: 3262-3270.
44. Pratz K, Cortes J, Roboz G, Rao N, Arowojolu O, Stine A et al. A pharmacodynamic study of the FLT3 inhibitor KW-2449 yields insight into the basis for clinical response. Blood 2009; 113: 3938-3946.
45. Levis M, Ravandi F, Wang ES, Baer MR, Perl A, Coutre S et al. Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse. Blood 2011; 117: 3294-3301.
46. Sato T, Yang X, Knapper S, White P, Smith BD, Galkin S et al. FLT3 ligand impedes the efficacy of FLT3 inhibitors in vitro and in vivo. Blood 2011; 117: 3286-3293.
47. Knapper S, White P, Levis MJ, Hills RK, Russell NH, Burnett A. The Efficacy of the FLT3 Inhibitor Lestaurtinib in AML Depends on Adequate Plasma Inhibitory Activity (PIA), and Is Unaffected by Rising FLT Ligand Levels: An Update of the NCRI AML15 & 17 Trials. Blood (ASH Annu Meet Abstr) 2011; 118: 421.
48. Zhang W, Konopleva M, Shi YX, McQueen T, Harris D, Ling X et al. Mutant FLT3: a direct target of sorafenib in acute myelogenous leukemia. J Natl Cancer Inst 2008; 100: 184-198.
49. Keir ST, Maris JM, Lock R, Kolb EA, Gorlick R, Carol H et al. Initial testing (stage 1) of the multi-targeted kinase inhibitor sorafenib by the pediatric preclinical testing program. Pediatr Blood Cancer 2010; 55: 1126-1133.
50. Hu S, Niu H, Minkin P, Orwick S, Shimada A, Inaba H et al. Comparison of antitumor effects of multitargeted tyrosine kinase inhibitors in acute myelogenous leukemia. Mol Cancer Ther 2008; 7: 1110-1120.
51. Goemans BF, Zwaan CM, Cloos J, de Lange D, Loonen AH, Reinhardt D et al. FLT3 and KIT mutated pediatric acute myeloid leukemia (AML) samples are sensitive in vitro to the tyrosine kinase inhibitor SU11657. Leuk Res 2010; 34: 1302-1307.
52. Ravandi F, Cortes JE, Jones D, Faderl S, Garcia-Manero G, Konopleva MY et al. Phase I/II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia. J Clin Oncol 2010; 28: 1856-1862.
53. Serve H, Wagner R, Sauerland C, Brunnberg U, Krug U, Schaich M et al. Sorafenib In Combination with Standard Induction and Consolidation Therapy In Elderly AML Patients: Results From a Randomized, Placebo-Controlled Phase II Trial. Blood (ASH Annu Meet Abstr) 2010; 116: 333.
54. Lacouture ME, Wu S, Robert C, Atkins MB, Kong HH, Guitart J et al. Evolving strategies for the management of hand-foot skin reaction associated with the multitargeted kinase inhibitors sorafenib and sunitinib. Oncologist 2008; 13: 1001-1011.
55. Moore AS, Faisal A, Gonzalez de Castro D, Bavetsias V, Sun C, Atrash B et al. Selective FLT3 inhibition of FLT3-ITD+ acute myeloid leukaemia resulting in secondary D835Y mutation: a model for emerging clinical resistance patterns. Leukemia 2012; 26: 1462-1470.
56. Williams AB, Nguyen B, Li L, Brown P, Levis M, Leahy D et al. Mutations of FLT3/ITD confer resistance to multiple tyrosine kinase inhibitors. Leukemia 2012; 27: 48-55.
57. Bain BJ. Leukaemia Diagnosis. 4 edn. (Wiley-Blackwell: Chichester, 2010.
58. Pollard JA, Alonzo TA, Loken M, Gerbing RB, Ho PA, Bernstein ID et al. Correlation of CD33 expression level with disease characteristics and response to gemtuzumab ozogamicin containing chemotherapy in childhood AML. Blood 2012; 119: 3705-3711.
59. Zwaan CM, Reinhardt D, Corbacioglu S, van Wering ER, Bokkerink JP, Tissing WJ et al. Gemtuzumab ozogamicin: first clinical experiences in children with relapsed/refractory acute myeloid leukemia treated on compassionate-use basis. Blood 2003; 101: 3868-3871.
60. Cooper TM, Franklin J, Gerbing RB, Alonzo TA, Hurwitz C, Raimondi SC et al. AAML03P1, a pilot study of the safety of gemtuzumab ozogamicin in combination with chemotherapy for newly diagnosed childhood acute myeloid leukemia: A report from the children's oncology group. Cancer 2011; 118: 761-769.
61. Satwani P, Bhatia M, Garvin Jr. JH, George D, Dela Cruz F, Le Gall J et al. A Phase I Study of Gemtuzumab Ozogamicin (GO) in Combination with Busulfan and Cyclophosphamide (Bu/Cy) and Allogeneic Stem Cell Transplantation in Children with Poor-Risk CD33(+) AML: A New Targeted Immunochemotherapy Myeloablative Conditioning (MAC) Regimen. Biol Blood Marrow Transplant 2011; 18: 324-329.
62. Zwaan CM, Reinhardt D, Zimmerman M, Hasle H, Stary J, Stark B et al. Salvage treatment for children with refractory first or second relapse of acute myeloid leukaemia with gemtuzumab ozogamicin: results of a phase II study. Br J Haematol 2010; 148: 768-776.
63. Aplenc R, Alonzo TA, Gerbing RB, Lange BJ, Hurwitz CA, Wells RJ et al. Safety and efficacy of gemtuzumab ozogamicin in combination with chemotherapy for pediatric acute myeloid leukemia: a report from the Children's Oncology Group. J Clin Oncol 2008; 26: 2390-3295.
64. Rubnitz JE, Inaba H, Dahl G, Ribeiro RC, Bowman WP, Taub J et al. Minimal residual disease-directed therapy for childhood acute myeloid leukaemia: results of the AML02 multicentre trial. Lancet Oncol 2010; 11: 543-552.
65. Wadleigh M, Richardson PG, Zahrieh D, Lee SJ, Cutler C, Ho V et al. Prior gemtuzumab ozogamicin exposure significantly increases the risk of venoocclusive disease in patients who undergo myeloablative allogeneic stem cell transplantation. Blood 2003; 102: 1578-1582.
66. Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH et al. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol 2011; 29: 369-377.
67. Cooper TM, Franklin J, Gerbing RB, Alonzo TA, Hurwitz C, Raimondi SC et al. AAML03P1, a pilot study of the safety of gemtuzumab ozogamicin in combination with chemotherapy for newly diagnosed childhood acute myeloid leukemia: a report from the Children's Oncology Group. Cancer 2012; 118: 761-769.
68. Jager E, van der Velden VH, te Marvelde JG, Walter RB, Agur Z, Vainstein V. Targeted drug delivery by gemtuzumab ozogamicin: mechanism-based mathematical model for treatment strategy improvement and therapy individualization. PLoS One 2011; 6: e24265.
69. Malfuson JV, Konopacki J, Thepenier C, Eddou H, Foissaud V, de Revel T. Fractionated doses of gemtuzumab ozogamicin combined with 3+7 induction chemotherapy as salvage treatment for young patients with acute myeloid leukemia in first relapse. Ann Hematol 2012; 91: 1871-1877.
70. Castaigne S, Pautas C, Terre C, Raffoux E, Bordessoule D, Bastie JN et al. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet 2012; 379: 1508-1516.
71. Hasle H, Abrahamsson J, Forestier E, Ha SY, Heldrup J, Jahnukainen K et al. Gemtuzumab ozogamicin as postconsolidation therapy does not prevent relapse in children with AML: results from NOPHO-AML 2004. Blood 2012; 120: 978-984.
72. Guzman ML, Swiderski CF, Howard DS, Grimes BA, Rossi RM, Szilvassy SJ et al. Preferential induction of apoptosis for primary human leukemic stem cells. Proc Natl Acad Sci USA 2002; 99: 16220-16225.
73. Horton TM, Pati D, Plon SE, Thompson PA, Bomgaars LR, Adamson PC et al. A phase 1 study of the proteasome inhibitor bortezomib in pediatric patients with refractory leukemia: a Children's Oncology Group study. Clin Cancer Res 2007; 13: 1516-1522.
74. Attar EC, De Angelo DJ, Supko JG, D'Amato F, Zahrieh D, Sirulnik A et al. Phase I and pharmacokinetic study of bortezomib in combination with idarubicin and cytarabine in patients with acute myelogenous leukemia. Clin Cancer Res 2008; 14: 1446-1454.
75. Messinger Y, Gaynon P, Raetz E, Hutchinson R, Dubois S, Glade-Bender J et al. Phase I study of bortezomib combined with chemotherapy in children with relapsed childhood acute lymphoblastic leukemia (ALL): a report from the therapeutic advances in childhood leukemia (TACL) consortium. Pediatr Blood Cancer 2010; 55: 254-259.
76. Carmena M, Earnshaw WC. The cellular geography of aurora kinases. Nat Rev Mol Cell Biol 2003; 4: 842-854.
77. Moore AS, Blagg J, Linardopoulos S, Pearson AD. Aurora kinase inhibitors: novel small molecules with promising activity in acute myeloid and Philadelphiapositive leukemias. Leukemia 2010; 24: 671-678.
78. Lowenberg B, Muus P, Ossenkoppele G, Rousselot P, Cahn JY, Ifrah N 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; 118: 6030-6036.
79. Grundy M, Seedhouse C, Shang S, Richardson J, Russell N, Pallis M. 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: 661-672.
80. Hartsink-Segers SA, Zwaan CM, Exalto C, Luijendijk MW, Calvert VS, Petricoin EF et al. Aurora kinases in childhood acute leukemia: the promise of aurora B as therapeutic target. Leukemia 2012; 27: 560-568.
81. Goldberg SL, Fenaux P, Craig MD, Gyan E, Lister J, Kassis J et al. Phase 2 Study of MLN8237, An Investigational Aurora A Kinase (AAK) Inhibitor In Patients with Acute Myelogenous Leukemia (AML) or Myelodysplastic Syndromes (MDS). Blood (ASH Annu Meet Abstr) 2010; 116: 3273.
82. Maris JM, Morton CL, Gorlick R, Kolb EA, Lock R, Carol H et al. Initial testing of the aurora kinase A inhibitor MLN8237 by the Pediatric Preclinical Testing Program (PPTP). Pediatr Blood Cancer 2010; 55: 26-34.
83. Wen Q, Goldenson B, Silver SJ, Schenone M, Dancik V, Huang Z et al. Identification of regulators of polyploidization presents therapeutic targets for treatment of AMKL. Cell 2012; 150: 575-589.
84. Gilliland DG, Griffin JD. The roles of FLT3 in hematopoiesis and leukemia. Blood 2002; 100: 1532-1542.
85. Jing J, Greshock J, Holbrook JD, Gilmartin AG, Zhang X, McNeil E et al. Comprehensive Predictive Biomarker Analysis for MEK Inhibitor GSK1120212. Mol Cancer Ther 2011; 11: 720-729.
86. Borthakur G, Foran JM, Kadia T, Jabbour E, Wissel P, Cox D et al. GSK1120212, a MEK1/MEK2 Inhibitor, Demonstrates Acceptable Tolerability and Preliminary Activity In a Dose Rising Trial In Subjects with AML and Other Hematologic Malignancies. Blood (ASH Annu Meet Abstr) 2010; 116: 3281.
87. Krige D, Needham LA, Bawden LJ, Flores N, Farmer H, Miles LE et al. CHR-2797: an antiproliferative aminopeptidase inhibitor that leads to amino acid deprivation in human leukemic cells. Cancer research 2008; 68: 6669-6679.
88. Jenkins C, Hewamana S, Krige D, Pepper C, Burnett A. Aminopeptidase inhibition by the novel agent CHR-2797 (tosedostat) for the therapy of acute myeloid leukemia. Leuk Res 2011; 35: 677-681.
89. Lowenberg B, Morgan G, Ossenkoppele GJ, Burnett AK, Zachee P, Duhrsen U et al. Phase I/II clinical study of Tosedostat, an inhibitor of aminopeptidases, in patients with acute myeloid leukemia and myelodysplasia. J Clin Oncol 2010; 28: 4333-4338.
90. Mathisen MS, Ravandi F. Efficacy of tosedostat, a novel, oral agent for elderly patients with relapsed or refractory acute myeloid leukemia: a review of the Phase II OPAL trial. Future oncology 2012; 8: 351-357.
91. Beghini A, Ripamonti CB, Cairoli R, Cazzaniga G, Colapietro P, Elice F et al. KIT activating mutations: incidence in adult and pediatric acute myeloid leukemia, and identification of an internal tandem duplication. Haematologica 2004; 89: 920-925.
92. Balgobind BV, Hollink IH, Arentsen-Peters ST, Zimmermann M, Harbott J, Beverloo HB et al. Integrative analysis of type-I and type-II aberrations underscores the genetic heterogeneity of pediatric acute myeloid leukemia. Haematologica 2011; 96: 1478-1487.
93. Paschka P, Marcucci G, Ruppert AS, Mrozek K, Chen H, Kittles RA et al. 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: 3904-3911.
94. Goemans BF, Zwaan CM, Miller M, Zimmermann M, Harlow A, Meshinchi S et al. Mutations in KIT and RAS are frequent events in pediatric core-binding factor acute myeloid leukemia. Leukemia 2005; 19: 1536-1542.
95. Pollard JA, Alonzo TA, Gerbing RB, Ho PA, Zeng R, Ravindranath Y et al. Prevalence and prognostic significance of KIT mutations in pediatric patients with core binding factor AML enrolled on serial pediatric cooperative trials for de novo AML. Blood 2010; 115: 2372-2379.
96. Wang YY, Zhao LJ, Wu CF, Liu P, Shi L, Liang Y 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: 2450-2455.
97. Mpakou VE, Kontsioti F, Papageorgiou S, Spathis A, Kottaridi C, Girkas K et al. Dasatinib inhibits proliferation and induces apoptosis in the KASUMI-1 cell line bearing the t(8;21)(q22;q22) and the N822K c-kit mutation. Leuk Res 2012; 37: 175-182.
98. Kolb EA, Gorlick R, Houghton PJ, Morton CL, Lock RB, Tajbakhsh M et al. Initial testing of dasatinib by the pediatric preclinical testing program. Pediatr Blood Cancer 2008; 50: 1198-1206.
99. DiPersio JF, Micallef IN, Stiff PJ, Bolwell BJ, Maziarz RT, Jacobsen E et al. Phase III prospective randomized double-blind placebo-controlled trial of plerixafor plus granulocyte colony-stimulating factor compared with placebo plus granulocyte colony-stimulating factor for autologous stem-cell mobilization and transplantation for patients with non-Hodgkin's lymphoma. J Clin Oncol 2009; 27: 4767-4773.
100. DiPersio JF, Stadtmauer EA, Nademanee A, Micallef IN, Stiff PJ, Kaufman JL et al. Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in patients with multiple myeloma. Blood 2009; 113: 5720-5726.
101. Aabideen K, Anoop P, Ethell ME, Potter MN. The feasibility of plerixafor as a second-line stem cell mobilizing agent in children. J Pediatr Hematol Oncol 2011; 33: 65-67.
102. Hubel K, Fresen MM, Salwender H, Basara N, Beier R, Theurich S et al. Plerixafor with and without chemotherapy in poor mobilizers: results from the German compassionate use program. Bone Marrow Transplant 2011; 46: 1045-1052.
103. Uy GL, Rettig MP, Motabi IH, McFarland K, Trinkaus KM, Hladnik LM et al. A phase I/II study of chemosensitization with the CXCR4 antagonist plerixafor in relapsed or refractory acute myeloid leukemia. Blood 2012; 119: 3917-3924.
104. Ley TJ, Ding L, Walter MJ, McLellan MD, Lamprecht T, Larson DE et al. DNMT3A mutations in acute myeloid leukemia. N Engl J Med 2010; 363: 2424-2433.
105. Delhommeau F, Dupont S, Della Valle V, James C, Trannoy S, Masse A et al. Mutation in TET2 in myeloid cancers. N Engl J Med 2009; 360: 2289-2301.
106. Paschka P, Schlenk RF, Gaidzik VI, Habdank M, Kronke J, Bullinger L et al. IDH1 and IDH2 mutations are frequent genetic alterations in acute myeloid leukemia and confer adverse prognosis in cytogenetically normal acute myeloid leukemia with NPM1 mutation without FLT3 internal tandem duplication. J Clin Oncol 2010; 28: 3636-3643.
107. Weissmann S, Alpermann T, Grossmann V, Kowarsch A, Nadarajah N, Eder C et al. Landscape of TET2 mutations in acute myeloid leukemia. Leukemia 2012; 26: 934-942.
108. Metzeler KH, Walker A, Geyer S, Garzon R, Klisovic RB, Bloomfield CD et al. DNMT3A mutations and response to the hypomethylating agent decitabine in acute myeloid leukemia. Leukemia 2012; 26: 1106-1107.
109. Al-Ali HK, Jaekel N, Junghanss C, Maschmeyer G, Krahl R, Cross M et al. Azacitidine in patients with acute myeloid leukemia medically unfit for or resistant to chemotherapy: a multicenter phase I/II study. Leuk Lymphoma 2012; 53: 110-117.
110. Pollyea DA, Kohrt HE, Gallegos L, Figueroa ME, Abdel-Wahab O, Zhang B et al. Safety, efficacy and biological predictors of response to sequential azacitidine and lenalidomide for elderly patients with acute myeloid leukemia. Leukemia 2012; 26: 893-901.
111. Gottlicher M, Minucci S, Zhu P, Kramer OH, Schimpf A, Giavara S et al. Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. EMBO J 2001; 20: 6969-6978.
112. Xie C, Edwards H, Lograsso SB, Buck SA, Matherly LH, Taub JW et al. Valproic acid synergistically enhances the cytotoxicity of clofarabine in pediatric acute myeloid leukemia cells. Pediatr Blood Cancer 2012; 59: 1245-1251.
113. Xie C, Edwards H, Xu X, Zhou H, Buck SA, Stout ML et al. Mechanisms of synergistic antileukemic interactions between valproic acid and cytarabine in pediatric acute myeloid leukemia. Clin Cancer Res 2010; 16: 5499-5510.
114. Corsetti MT, Salvi F, Perticone S, Baraldi A, De Paoli L, Gatto S et al. Hematologic improvement and response in elderly AML/RAEB patients treated with valproic acid and low-dose Ara-C. Leuk Res 2011; 35: 991-997.
115. Lane S, Gill D, McMillan NA, Saunders N, Murphy R, Spurr T et al. Valproic acid combined with cytosine arabinoside in elderly patients with acute myeloid leukemia has in vitro but limited clinical activity. Leuk Lymphoma 2012; 53: 1077-1083.
116. Kuendgen A, Schmid M, Schlenk R, Knipp S, Hildebrandt B, Steidl C et al. The histone deacetylase (HDAC) inhibitor valproic acid as monotherapy or in combination with all-trans retinoic acid in patients with acute myeloid leukemia. Cancer 2006; 106: 112-119.
117. Blum W, Klisovic RB, Hackanson B, Liu Z, Liu S, Devine H et al. Phase I study of decitabine alone or in combination with valproic acid in acute myeloid leukemia. J Clin Oncol 2007; 25: 3884-3891.
118. Schaefer EW, Loaiza-Bonilla A, Juckett M, DiPersio JF, Roy V, Slack J et al. A phase 2 study of vorinostat in acute myeloid leukemia. Haematologica 2009; 94: 1375-1382.
119. Garcia-Manero G, Tambaro FP, Bekele NB, Yang H, Ravandi F, Jabbour E et al. Phase II trial of vorinostat with idarubicin and cytarabine for patients with newly diagnosed acute myelogenous leukemia or myelodysplastic syndrome. J Clin Oncol 2012; 30: 2204-2210.
120. Bernt KM, Armstrong SA. Targeting epigenetic programs in MLL-rearranged leukemias. Hematology Am Soc Hematol Educ Program 2011; 354-360.
121. Daigle SR, Olhava EJ, Therkelsen CA, Majer CR, Sneeringer CJ, Song J et al. Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor. Cancer Cell 2011; 20: 53-65.
122. Chen L, Deshpande AJ, Banka D, Bernt KM, Dias S, Buske C et al. Abrogation of MLL-AF10 and CALM-AF10-mediated transformation through genetic inactivation or pharmacological inhibition of the H3K79 methyltransferase Dot1l. Leukemia 2013; 27: 813-822.
123. Levis MJ, Perl AE, Dombret H, Dohner H, Steffen B, Rousselot P et al. Final Results of a Phase 2 Open-Label, Monotherapy Efficacy and Safety Study of Quizartinib (AC220) in Patients with FLT3-ITD Positive or Negative Relapsed/Refractory Acute Myeloid Leukemia After Second-Line Chemotherapy or Hematopoietic Stem Cell Transplantation. ASH Annu Meet Abstr 2012; 120: 673.
124. Podesta JE, Sugar R, Squires M, Linardopoulos S, Pearson AD, Moore AS. Adaptation of the plasma inhibitory activity assay to detect Aurora, ABL and FLT3 kinase inhibition by AT9283 in pediatric leukemia. Leuk Res 2011; 35: 1273-1275.
125. Moreno L, Pearson AD. How can attrition rates be reduced in cancer drug discovery? Expert Opin Drug Discov 2013; 8: 363-368.