Best Practice & Research Clinical Haematology
Volume 20, Issue 1 , Pages 39-48 , March 2007

Targeted agents in AML: much more to do

  • Richard M. Stone, MD (Clinical Director and Associate Professor of Medicine)

      Affiliations

    • Corresponding Author InformationTel.: +1 617 632 2214; Fax: +1 617 632 2933.

References 

  1. Kelly LM, Gilliland DG. Genetics of myeloid leukemias. Annual Review of Genomics and Human Genetics. 2002;3:179–198
  2. Gilliland DG, Griffin JD. The roles of FLT3 in hematopoiesis and leukemia. Blood. 2002;100:1532–1542
  3. Reuter CW, Morgan MA, Bergmann L. Targeting the Ras signaling pathway: a rational, mechanism-based treatment for hematologic malignancies?. Blood. 2000;96:1655–1669
  4. Egger G, Liang G, Aparicio A, Jones PA. Epigenetics in human disease and prospects for epigenetic therapy. Nature. 2004;429:457–463
  5. Del Poeta G, Venditti A, Del Principe MI, et al. Amount of spontaneous apoptosis detected by Bax/Bcl-2 ratio predicts outcome in acute myeloid leukemia (AML). Blood. 2003;101:2125–2131
  6. Matsunaga T, Takemoto N, Sato T, et al. Interaction between leukemic-cell VLA-4 and stromal fibronectin is a decisive factor for minimal residual disease of acute myelogenous leukemia. Nature Medicine. 2003;9:1158–1165
  7. Radich JP, Kopecky KJ, Willman CL, et al. N-ras mutations in adult de novo acute myelogenous leukemia: prevalence and clinical significance. Blood. 1990;76:801–807
  8. Lancet JE, Karp JE. Farnesyltransferase inhibitors in hematologic malignancies: new horizons in therapy. Blood. 2003;102:3880–3889
  9. Karp JE, Lancet JE, Kaufmann SH, 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
  10. Harousseau J-L, Reiffers J, Lowenberg B, et al. Zarnestra(TM) (R115777) in patients with relapsed and refractory acute myelogenous leukemia (AML): results of a multicenter phase 2 study. Blood. 2003;102:177a;(abstract 614)
  11. Lancet JE, Gojo I, Gotlib J, et al. Tipifarnib (ZARNESTRA™) in previously untreated poor-riskAML and MDS: Interim results of a phase 2 trial. Blood. 2004;102:176a;(abstract 874)
  12. Gilliland DG, Griffin JD. Role of FLT3 in leukemia. Current Opinion in Hematology. 2002;9:274–281
  13. Kottaridis 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
  14. Whitman SP, Archer KJ, Feng L, 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 Research. 2001;61:7233–7239
  15. 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
  16. Kelly LM, Liu Q, Kutok JL, et al. FLT3 internal tandem duplication mutations associated with human acute myeloid leukemias induce myeloproliferative disease in a murine bone marrow transplant model. Blood. 2002;99:310–318
  17. Kelly LM, Yu JC, Boulton CL, et al. CT53518, a novel selective FLT3 antagonist for the treatment of acute myelogenous leukemia (AML). Cancer Cell. 2002;1:421–432
  18. DeAngelo DJ, Stone RM, Bruner RJ, et al. Phase I clinical results with MLN518, a novel FLT3 antagonist: tolerability, pharmacokinetics, and pharmacodynamics. Blood. 2003;102:65a;(abstract 219)
  19. De Angelo DJ, Stone R, Heaney ML, et al. Phase II Evaluation of the Tyrosine Kinase Inhibitor MLN518 in Patients with Acute Myeloid Leukemia (AML) Bearing a FLT3 Internal Tandem Duplication (ITD) Mutation. Blood. 2004;104:496a;(abstract 1792) Ref Type: Abstract
  20. 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
  21. Stone RM, DeAngelo DJ, 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
  22. Heidel F, Solem FK, Breitenbuecher F, 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
  23. Propper DJ, McDonald AC, Man A, et al. Phase I and pharmacokinetic study of PKC412, an inhibitor of protein kinase C. Journal of Clinical Oncology. 2001;19:1485–1492
  24. Levis M, Pham R, Smith BD, et al. In vitro studies of a FLT3 inhibitor combined with chemotherapy: sequence of administration is important to achieve synergistic cytotoxic effects. Blood. 2004;104:1145–1150
  25. Stone R, Fischer T, Paquette R, et al. Phase IB Study of PKC412, an Oral FLT3 kinase inhibitor, in sequential and simultaneous combinations with Daunorubicin and Cytarabine (DA) induction and high-dose cytarabine consolidation in newly diagnosed patients with AML. Blood. 2005;106:121a;(abstract 404) Ref Type: Abstract
  26. Levis M, Stine A, Pham R, et al. Pharmacokinetic and Pharmacodynamic Studies of Lestaurtinib (CEP-701) and PKC-412: Cytotoxicity Is Often Dependent on Non-FLT3-Mediated Effects. Blood. 2005;106:692a;(abstract 2463) Ref Type: Abstract
  27. George P, Bali P, Cohen P, et al. Cotreatment with 17-allylamino-demethoxygeldanamycin and FLT-3 kinase inhibitor PKC412 is highly effective against human acute myelogenous leukemia cells with mutant FLT-3. Cancer Research. 2004;64:3645–3652
  28. Greenberg PL, Lee SJ, Advani R, et al. Mitoxantrone, etoposide, and cytarabine with or without valspodar in patients with relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome: a phase III trial (E2995). Journal of Clinical Oncology. 2004;22:1078–1086
  29. Baer MR, George SL, Dodge RK, et al. Phase 3 study of the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age and older with acute myeloid leukemia: Cancer and Leukemia Group B Study 9720. Blood. 2002;100:1224–1232
  30. List AF, Kopecky KJ, Willman CL, et al. Benefit of cyclosporine modulation of drug resistance in patients with poor-risk acute myeloid leukemia: a Southwest Oncology Group study. Blood. 2001;98:3212–3220
  31. Marcucci G, Stock W, Dai G, et al. G3139, a BCL-2 antisense oligo-nucleotide, in AML. Annals of Hematology. 2004;83(supplement 1):S93–S94
  32. Karp JE, Gojo I, Pili R, et al. Targeting vascular endothelial growth factor for relapsed and refractory adult acute myelogenous leukemias: therapy with sequential 1-beta-d-arabinofuranosylcytosine, mitoxantrone, and bevacizumab. Clinical Cancer Research. 2004;10:3577–3585
  33. Rowe JM, 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
  34. Lowenberg B, van Putten W, Theobald M, et al. Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia. The New England Journal of Medicine. 2003;349:743–752
  35. Bross PF, Beitz J, Chen G, et al. Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia. Clinical Cancer Research. 2001;7:1490–1496
  36. Wadleigh M, Richardson PG, Zahrieh D, et al. Prior gemtuzumab ozogamicin exposure significantly increases the risk of veno-occlusive disease in patients who undergo myeloablative allogeneic stem cell transplantation. Blood. 2003;102:1578–1582
  37. Feldman EJ, Brandwein J, Stone R, et al. Phase III randomized multicenter study of a humanized anti-CD33 monoclonal antibody, lintuzumab, in combination with chemotherapy, versus chemotherapy alone in patients with refractory or first-relapsed acute myeloid leukemia. Journal of Clinical Oncology. 2005;23:4110–4116
  38. Frankel AE, Hall PD, Burbage C, et al. Modulation of the apoptotic response of human myeloid leukemia cells to a diphtheria toxin granulocyte-macrophage colony-stimulating factor fusion protein. Blood. 1997;90:3654–3661
  39. Heslop HE, Stevenson FK, Molldrem JJ. Immunotherapy of hematologic malignancy. Hematology/the Education Program of the American Society of Hematology. 2003;331–349
  40. Gong J, Koido S, Kato Y, et al. Induction of anti-leukemic cytotoxic T lymphocytes by fusion of patient-derived dendritic cells with autologous myeloblasts. Leukemia Research. 2004;28:1303–1312
  41. Alyea EP, Kim HT, Ho V, et al. Comparative outcome of nonmyeloablative and myeloablative allogeneic hematopoietic cell transplantation for patients older than 50 years of age. Blood. 2005;105:1810–1814
  42. Kantarjian H, Gandhi V, Cortes J, et al. Phase 2 clinical and pharmacologic study of clofarabine in patients with refractory or relapsed acute leukemia. Blood. 2003;102:2379–2386
  43. Giles FJ, Feldman EJ, Roboz GJ, et al. Phase II study of troxacitabine, a novel dioxolane nucleoside analog, in patients with untreated or imatinib mesylate-resistant chronic myelogenous leukemia in blastic phase. Leukemia Research. 2003;27:1091–1096
  44. Giles F, Thomas D, Garcia-Manero G, et al. A Phase I and pharmacokinetic study of VNP40101M, a novel sulfonylhydrazine alkylating agent, in patients with refractory leukemia. Clinical Cancer Research. 2004;10:2908–2917
  45. 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;105:940–947

PII: S1521-6926(06)00086-7

doi: 10.1016/j.beha.2006.11.006

Best Practice & Research Clinical Haematology
Volume 20, Issue 1 , Pages 39-48 , March 2007

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