FLT3 inhibition as a targeted therapy for acute myeloid leukemia

Current Opinion in Oncology

Volumn 21, Issue 6, 2009, Pages 594-600

  Sanz, Miguel ^a   Burnett, Alan ^b   Lo Coco, Francesco ^c   Lowenoerg, Bob ^d  

^a HOSPITAL UNIVERSITARIO LA FE   (Spain)

^b CARDIFF UNIVERSITY   (United Kingdom)

^c UNIVERSITY OF ROME TOR VERGATA   (Italy)

^d ERASMUS MEDICAL CENTER   (Netherlands)

Author keywords

Acute myeloid leukaemia; FLT3; Tyrosine kinase

Indexed keywords

4 [N (2 HYDROXYETHYL) N [2 (3 INDOLYL)ETHYL]AMINOMETHYL]CINNAMOHYDROXAMIC ACID; ANTINEOPLASTIC AGENT; CISPLATIN; CYTARABINE; FLT3 LIGAND; GEMCITABINE; LESTAURTINIB; MIDOSTAURIN; RAPAMYCIN; SORAFENIB; SUNITINIB; TANDUTINIB; TANESPIMYCIN; CARBAZOLE DERIVATIVE; CD135 ANTIGEN; DRUG DERIVATIVE; FLT3 PROTEIN, HUMAN; STAUROSPORINE;

ACUTE GRANULOCYTIC LEUKEMIA; CANCER CHEMOTHERAPY; CANCER RELAPSE; CANCER SURVIVAL; CLINICAL TRIAL; DIARRHEA; DRUG ANTAGONISM; DRUG EFFICACY; DRUG INHIBITION; DRUG SAFETY; DRUG TOLERABILITY; FATIGUE; GENE MUTATION; GENE TARGETING; HUMAN; LUNG NON SMALL CELL CANCER; MEDICAL DECISION MAKING; MUSCLE WEAKNESS; NAUSEA AND VOMITING; NONHUMAN; PRIORITY JOURNAL; REVIEW; TREATMENT OUTCOME; TREATMENT RESPONSE; ACUTE DISEASE; ANIMAL; CHEMICAL STRUCTURE; CHEMISTRY; DRUG SCREENING; GENETICS; METABOLISM; MUTATION; MYELOID LEUKEMIA; PATHOLOGY;

ACUTE DISEASE; ANIMALS; CARBAZOLES; DRUG EVALUATION, PRECLINICAL; FMS-LIKE TYROSINE KINASE 3; HUMANS; LEUKEMIA, MYELOID; MOLECULAR STRUCTURE; MUTATION; STAUROSPORINE;

EID: 74049141397     PISSN: 10408746     EISSN: None     Source Type: Journal    
DOI: 10.1097/CCO.0b013e32833118fd     Document Type: Review

References (60)

1. Hann IM, Stevens RF, Goldstone AH, et al. Randomized comparison of DAT versus ADE as induction chemotherapy In children and younger adults with acute myeloid leukemia. Results of the Medical Research Council's 10th AML Trial (MRC AML10). Blood 1997; 89:2311-2318.
2. Goldstone AH, Burnett AK, Wheatley K, et al. Attempts to Improve treatment outcomes in acute myeloid leukemia (AML) In older patients: the results of the United Kingdom Medical Research Council AML11 trial. Blood 2001 ;98:1302-1311.
3. RoweJM, Neuberg D, Friedenberg W, et al. A phase 3 study of three induction regimens and of priming with GM-CSF In older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group. Blood 2004; 103:479-485.
4. Lowenberg B, Downing JR, Burnett A. Acute myeloid leukemia. N Engl J Med 1999;341:1051-1062.
5. Grimwade D, Walker H, Oliver F, et al. The importance of diagnostic cytogenetics on outcome In AML: analysis of 1612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children's Leukaemia Working Parties. Blood 1998; 92:2322-2333. (Pubitemid 28452973)
6. Byrd JC, Mrozek K, Dodge RK, et al. Pretreatment cytogenetic abnormalities are predictive of Induction success, cumulative Incidence of relapse, and overall survival In adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood 2002; 100:4325-4336. (Pubitemid 35429670)
7. Mrozek K, Bloomfleld CD. Chromosome aberrations, gene mutations and expression changes, and prognosis In adult acute myeloid leukemia. Hematol Am Soo Hematol Eduo Program 2006: 169-1 77.
8. Slovak ML, Kopecky KJ, Casslleth PA, et al. Karyotype analysis predicts outcome of preremisslon and postremisslon therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative OncologyGroup Study. Blood 2000; 96:4075-4083.
9. Cornelissen JJ, van Putten WL, Verdonok LF, et al. Results of a HOVON/SAKK donor versus no-donor analysis of myeloablatlve HLA-identlcal sibling stem cell transplantation In first remission acute myeloid leukemia in young and middle-aged adults: benefits for whom? Blood 2007; 109:3658-3666.
10. Löwenberg B. Diagnosis and prognosis in acute myeloid leukemia: the art of distinction. New Engl J Med 2008; 358:1960-1962. (Pubitemid 351620119)
11. Sohlenk RF, Döhner K, Krauter J, et al. Mutations and treatment outcome in cytogenetically normai cute myeloid leukemia. New Engl J Med 2008; 358:1909-1918. (Pubitemid 351620111)
12. Fallni B, Mecucci C, Tiacci E, et al. Cytoplasmic nucleophosmin In acute myelogenous leukemia with a normal karyotype. N Engl J Med 2005; 352: 254-266. (Pubitemid 40110814)
13. Dohner K, Sohlenk RF, Habdank M, et al. Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics: Interaction with other gene mutations. Blood 2005; 106:3740-3746. (Pubitemid 41739007)
14. Verhaak RG, Goudswaard CS, van Putten W, et al. Mutations In nucleo- phosmin (NPM1) In acute myeloid leukemia (AML): association with other gene abnormalities and previously established gene expression signatures and their favorable prognostic significance. Blood 2005; 106:3747-3754.
15. Small D. FLT3 mutations: biology and treatment. Hematol Am Soc Hematol Educ Program 2006: 178-184.
16. Meshinohl S, Woods WG, Stirewalt DL, et al. Prevalence and prognostic significance of Flt3 Internal tandem duplication in pediatric acute myeloid leukemia. Blood 2001; 97:89-94. (Pubitemid 32061246)
17. Kottaridls PD, Gale RE, Frew ME, et al. The presence of a FLT3 Internal tandem duplication in patients with acute myeloid leukemia (AML) adds Important prognostic Information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood 2001; 98:1752-1759.
18. Stirewalt DL, Kopecky KJ, Meshlnchi S, et al. Size of FLT3 internal tandem duplication has prognostic significance In patients with acute myeloid leu- kemia. Blood 2006; 107:3724-3726.
19. VaIk PJ, Verhaak RG, Beijen MA, et al. Prognostically useful gene-expression profiles In acute myeloid leukemia. N Engl J Med 2004; 350:161 7-1628.
20. Kelly LM, Gllliland DG. Genetics of myeloid leukemias. Annu Rev Genomics Hum Genet 2002; 3:179-198.
21. Mrózek K, Marcucci G, Paschka P, et al. Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cyto- genetics: are we ready for a prognostically prioritized molecular classifica- tion? Blood 2007; 109:431-448.
22. Advani AS. FLT3 and acute myelogenous leukemia: biology, clinical signifi- cance and therapeutic applications. Curr Pharm Des 2005; 11:3349-3357.
23. Nakao M, Yokota S, Iwal T, et al. Internal tandem duplication of the flt3 gene found in acute myeloid leukemia. Leukemia 1996; 10:1911-1918. (Pubitemid 27019637)
24. Krause DS, Van Etten RA. Tyrosine kinases as targets for cancer therapy. N Engl J Med 2005; 353:1 72-187.
25. Whltesell L, Lindqulst SL HSP90 and the chaperoning of cancer. Nat Rev Cancer 2005; 5:761-772.
26. Carow CE, Levensteln M, Kaufmann SH, et al. Expression of the hemato- poietic growth factor receptor FLT3 (STK-1/Flk2) in human leukemias. Blood 1996; 87:1089-1096.
27. Zheng R, Levis M, Piloto O, et al. FLT3 ligand causes autocrine signaling In acute myeloid leukemia cells. Blood 2004; 103:267-274. (Pubitemid 38029948)
28. Yamamoto Y, Kiyol H, Nakano Y, et al. Activating mutation of D835 within the activation loop of FLT3 In human hematologic malignancies. Blood 2001 ; 97:2434-2439. (Pubitemid 32291491)
29. Griffith J, Black J, Faerman C, et al. The structural basis for autoinhibition of FLT3 by the juxtamembrane domain. Mol Cell 2004; 13:169-178. (Pubitemid 38183264)
30. Piloto O, Nguyen B, Huso D, et al. IMC-EB10, an antl-FLT3 monoclonal antibody, prolongs survival and reduces nonobese diabetic/severe combined immunodeflcient engraftment of some acute lymphoblastic leukemia cell lines and primary leukemic samples. Cancer Res 2006; 66:4843-4851.
31. Piloto O, Levis M, Huso D, et al. Inhibitory anti-FLT3 antibodies are capable of mediating antibody-dependent cell-mediated cytotoxicity and reducing en- graftment of acute myelogenous leukemia blasts in nonobese diabetic/severe combined immunodeflcient mice. Cancer Res 2005; 65:1514-1522. (Pubitemid 40276832)
32. Li Y, Li H, Wang MN, et al. Suppression of leukemia expressing wild-type or ITD-mutant FLT3 receptor by a fully human antl-FLT3 neutralizing antibody. Blood 2004; 104:1137-1144. (Pubitemid 39038035)
33. George P, Bali P, Cohen P, et al. Cotreatment with 1 7-allylamino- demethox- ygeldanamycln and FLT-3 kinase inhibitor PKC412 is highly effective against human acute myelogenous leukemia cells with mutant FLT-3. Cancer Res 2004; 64:3645-3652. (Pubitemid 38657944)
34. Zhao M, Kiyol H, Yamamoto Y, et al. In vivo treatment of mutant FLT3- transformed murine leukemia with a tyrosine kinase inhibitor. Leukemia 2000; 14:374-378.
35. Yao Q, Nishluchi R, Li Q, et al. FLT3 expressing leukemias are selectively sensitive to inhibitors of the molecular chaperone heat shock protein 90 through destabilizatlon of signal transduction-assoclated kinases. Clin Can- cer Res 2003; 9:4483-4493. (Pubitemid 37248407)
36. Minami Y, Kiyoi H, Yamamoto Y, et al. Selective apoptosis of tandemly duplicated FLT3-transformed leukemia cells by Hsp90 Inhibitors. Leukemia 2002; 16:1535-1540. (Pubitemid 34906059)
37. George P, Bali P, Annavarapu S, et al. Combination of the histone deaoetylase inhibitor LBH589 and the hsp90 inhibitor 1 7-AAG Is highly active against human CML-BC cells and AML cells with activating mutation of FLT-3. Blood 2005; 105:1768-1776. (Pubitemid 40223701)
38. Karaman MW, Herrgard S, Treiber DK, et al. A quantitative analysis of kinase • inhibitor selectivity. Nat Bioteohnol 2008; 26:127-132.
39. Baselga J. Targeting tyrosine kinases in cancer: the second wave. Science 2006;312:1175-1178. (Pubitemid 43801135)
40. Hexner EO, Serdikoff C, Jan M, et al. Lestaurtinib (CEP701 ) is a JAK2 inhibitor that suppresses JAK2/STAT5 signaling and the proliferation of primary erythroid cells from patients with myeloproliferative disorders. Blood 2008; 111:5663-5671.
41. Pardanan A, Hood J, Lasho T, et al. TG101209, a small JAK2-selective kinase inhibitor potently inhibits myeloproliferative disorder-associated JAK2V61 7F and MPLW515L/K mutations. Leukemia 2007; 21:1658-1668. (Pubitemid 47086756)
42. Levis M, Allebach J, Tse KF, et al. A FLT3-targeted tyrosine kinase inhibitor is cytotoxic to leukemia cells In vitro and In vivo. Blood 2002; 99:3885-3891.
43. Weisberg E, Boulton C, Kelly LM, et al. Inhibition of mutant FLT3 receptors in leukemia cells by the small molecule tyrosine kinase inhibitor PKC412. Cancer Cell 2002; 1:433-443. (Pubitemid 41039124)
44. Revill P, Serradell N, Bolós J, Rosa E. Lestaurtinib. Multlkinase inhibitor, oncolytic, antlpsoriatic agent. Drugs Fut 2007; 32:215-222.
45. Knapper S, Mills Kl, Gillkes AF, et al. The effects of lestaurtinib (CEP701 ) and PKC412 on primary AML blasts: the induction of cytotoxicity varies with dependence on FLT3 signaling In both FLT3-mutated and wild-type cases. Blood 2006; 108:3494-3503. (Pubitemid 44776892)
46. Pratz K, Levis M. Incorporating FLT3 inhibitors into acute myeloid leukemia treatment regimens. Leuk Lymphoma 2008; 49:852-863. (Pubitemid 351942737)
47. Stone R, DeAngelo D, Klimek V, et al. Patients with acute myeloid leukemia and an activating mutation in FLT3 respond to a small-molecule FLT3 tyrosine kinase Inhibitor, PKC412. Blood 2005; 105:54-60. (Pubitemid 40053063)
48. Knapper S, Burnett AK, Llttlewood T, et al. A phase 2 trial of the FLT3 inhibitor lestaurtlnib (CEP701) as first-line treatment for older patients with acute myeloid leukemia not considered fit for Intensive chemotherapy. Blood 2006; 108:3262-3270.
49. DeAngelo DJ, Stone RM, Heaney ML, et al. Phase 1 clinical results with tandutlnib (MLN51 8), a novel FLT3 antagonist, in patients with acute myelogenous leukemia or high-risk myelodysplastlc syndrome: safety, pharmacokinetics, and pharmacodynamics. Blood 2006; 108:3674-3681.
50. Fiedler W, Serve H, Döhner H, et al. A phase I study of SU11248 In the treatment of patients with refractory or resistant acute myeloid leukemia (AML) or not amenable to conventional therapy for the disease. Blood 2005; 105:986-993.
51. Quintas-CardamaA, Kantarjlan H, Andreef M, et al. Phase I trial of intermittent administration of sorafenib (BAY 43-9006) for patients (pts) with refractory/ relapsed acute myelogenous leukemia (AML) [abstract]. J Clin Oncol 2007; 25 (18suppl):7018.
52. Bali P, George P, Cohen P, et al. Superior activity of the combination of histone deaoetylase inhibitor LAQ824 and the FLT-3 kinase inhibitor PKC412 against human acute myelogenous leukemia cells with mutant FLT-3. Clin Cancer Res 2004; 10:4991-4997. (Pubitemid 39099772)
53. Mohi MG, Boulton C, Gu TL, et al. Combination of rapamyoin and protein tyrosine kinase (PTK) inhibitors for the treatment of leukemias caused by oncogenic PTKs. Proo Natl Acad Sol USA 2004; 101 :3130-3135. (Pubitemid 38327746)
54. Monnerat C, Henriksson R, Le Chevalier T, et al. Phase I study of PKC412 (N- benzoyl-staurosporine), a novel oral protein kinase C inhibitor, combined with gemcitablne and cisplatin In patients with nonsmall-cell lung cancer. Ann Oncol 2004; 15:316-323. (Pubitemid 38262634)
55. Stone RM, Fischer T, Paquette R, et al. Phase 1B study of PKC412, an oral FLT3 kinase inhibitor, in sequential and simultaneous combinations with daunorubicln and oytarabine (DA) induction and high-dose oytarabine con- solidation in newly-diagnosed adult patients (PTS) with acute myeloid leu- kemia (AML) under age. Blood 2006; 61:108; Abstract 157.
56. Smith BD, Levis M, Beran M, 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. (Pubitemid 38596280)
57. Levis M, Brown P, Smith BD, 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. (Pubitemid 44776890)
58. Levis M, Pham R, Smith BD, Small D. In vitro studies of a FLT3 inhibitor combined with chemotherapy: sequence of administration Is important to achieve synergistic cytotoxic effects. Blood 2004; 04:1145-1150.
59. Levis M, Smith BD, Beran M, et al. A randomized, open-label study of lestaurtinib (CEP-701), an oral FLT3 inhibitor, administered in sequence with chemotherapy in patients with relapsed AML harboring FLT3 activating mutations: clinical response correlates with successful FLT3 inhibition. Blood 2005; 106 [Abstract 403].
60. DeAngelo D, Amrein PC, Kovaosovios TJ, et al. Phase 1/2 study of tandutinib (MLN518) plus standard induction chemotherapy In newly diagnosed acute myelogenous leukemia (AML). Blood 2006; 108:51a.