Leukemia Research
Volume 34, Issue 10 , Pages 1302-1307 , October 2010

FLT3 and KIT mutated pediatric acute myeloid leukemia (AML) samples are sensitive in vitro to the tyrosine kinase inhibitor SU11657

  • Bianca F. Goemans

      Affiliations

    • Pediatric Oncology and Hematology, VU University Medical Center, Amsterdam, The Netherlands
    • Corresponding Author InformationCorresponding author at: Department of Pediatric Hematology and Oncology, VU University Medical Center, POB 7057, 1007 MB Amsterdam, The Netherlands. Tel.: +31 20 4442420; fax: +31 20 4442422.
    • ,
  • Christian M. Zwaan

      Affiliations

    • Pediatric Oncology and Hematology, Erasmus MC, Sophia Children's Hospital, Rotterdam, The Netherlands
    • ,
  • Jacqueline Cloos

      Affiliations

    • Pediatric Oncology and Hematology, VU University Medical Center, Amsterdam, The Netherlands
    • ,
  • Desiree de Lange

      Affiliations

    • Pediatric Oncology and Hematology, VU University Medical Center, Amsterdam, The Netherlands
    • ,
  • Anne H. Loonen

      Affiliations

    • Pediatric Oncology and Hematology, VU University Medical Center, Amsterdam, The Netherlands
    • ,
  • Dirk Reinhardt

      Affiliations

    • AML-BFM Study Group, Hannover Medical School, Hannover, Germany
    • ,
  • Karel Hählen

      Affiliations

    • Pediatric Oncology and Hematology, Erasmus MC, Sophia Children's Hospital, Rotterdam, The Netherlands
    • DCOG, The Hague, The Netherlands
    • ,
  • Brenda E.S. Gibson

      Affiliations

    • UK Childhood Leukaemia Working Party, United Kingdom
    • ,
  • Ursula Creutzig

      Affiliations

    • AML-BFM Study Group, Hannover Medical School, Hannover, Germany
    • ,
  • Gertjan J.L. Kaspers

      Affiliations

    • Pediatric Oncology and Hematology, VU University Medical Center, Amsterdam, The Netherlands

Received 4 November 2009 ,Revised 20 March 2010 ,Accepted 8 April 2010.

References 

  1. Kaspers GJ, Creutzig U. Pediatric acute myeloid leukemia: international progress and future directions. Leukemia. 2005;19:2025–2029
  2. Zwaan CM, Meshinchi S, Radich JP, et al. FLT3 internal tandem duplication in 234 children with acute myeloid leukemia: prognostic significance and relation to cellular drug resistance. Blood. 2003;102:2387–2394
  3. Meshinchi 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
  4. Meshinchi S, Alonzo TA, Stirewalt DL, et al. Clinical implications of FLT3 mutations in pediatric AML. Blood. 2006;108:3654–3661
  5. Stirewalt DL, Kopecky KJ, Meshinchi S, et al. Size of FLT3 internal tandem duplication has prognostic significance in patients with acute myeloid leukemia. Blood. 2006;107:3724–3726
  6. Kusec R, Jaksic O, Ostojic S, et al. More on prognostic significance of FLT3/ITD size in acute myeloid leukemia (AML). Blood. 2006;108:405–406
  7. Ponziani V, Gianfaldoni G, Mannelli F, et al. The size of duplication does not add to the prognostic significance of FLT3 internal tandem duplication in acute myeloid leukemia patients. Leukemia. 2006;20:2074–2076
  8. Kayser S, Schlenk RF, Londono MC, et al. Insertion of FLT3 internal tandem duplication in the tyrosine kinase domain-1 is associated with resistance to chemotherapy and inferior outcome. Blood. 2009;114:2386–2392
  9. Goemans BF, Zwaan C, Miller M, et al. Mutations in KIT and RAS are frequent events in pediatric core-binding factor acute myeloid leukemia. Leukemia. 2005;19:1536–1542
  10. Corbacioglu S, Kilic M, Westhoff MA, et al. Newly identified c-kit receptor tyrosine kinase ITD in childhood AML induces ligand independent growth and is responsive to a synergistic effect of imatinib and rapamycin. Blood. 2006;108:3504–3513
  11. Beghini A, Ripamonti CB, Cairoli R, 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
  12. Boissel N, Leroy H, Brethon B, et al. Incidence and prognostic impact of c-Kit, FLT3, and Ras gene mutations in core binding factor acute myeloid leukemia (CBF-AML). Leukemia. 2006;20:965–970
  13. Cairoli R, Beghini A, Grillo G, et al. Prognostic impact of c-KIT mutations in core binding factor leukemias: an Italian retrospective study. Blood. 2006;107:3463–3468
  14. Paschka P, Marcucci G, Ruppert AS, 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
  15. Shimada A, Taki T, Tabuchi K, et al. KIT mutations, and not FLT3 internal tandem duplication, are strongly associated with a poor prognosis in pediatric acute myeloid leukemia with t(8;21): a study of the Japanese Childhood AML Cooperative Study Group. Blood. 2006;107:1806–1809
  16. Kantarjian H, Sawyers C, Hochhaus A, et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med. 2002;346:645–652
  17. O’Brien SG, Guilhot F, Larson RA, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003;348:994–1004
  18. De Angelo DJ, Stone RM, Heaney ML, et al. Phase I clinical results with tandutinib (MLN518), a novel FLT3 antagonist, in patients with acute myelogenous leukemia or high-risk myelodysplastic syndrome: safety, pharmacokinetics, and pharmacodynamics. Blood. 2006;108:3674–3681
  19. 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
  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. Zhang W, Konopleva M, Shi Y, et al. Sorafenib (BAY 43-9006) directly targets FLT3-ITD in acute myelogenous leukemia. Blood. 2006;108:255
  22. Mendel DB, Laird AD, Xin X, et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res. 2003;9:327–337
  23. O’Farrell AM, Abrams TJ, Yuen HA, et al. SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood. 2003;101:3597–3605
  24. Fabian MA, Biggs WH, Treiber DK, et al. A small molecule–kinase interaction map for clinical kinase inhibitors. Nat Biotechnol. 2005;23:329–336
  25. Goodman VL, Rock EP, Dagher R, et al. Approval summary: sunitinib for the treatment of imatinib refractory or intolerant gastrointestinal stromal tumors and advanced renal cell carcinoma. Clin Cancer Res. 2007;13:1367–1373
  26. Fiedler W, Serve H, Dohner H, et al. A phase 1 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
  27. Cain JA, Grisolano JL, Laird AD, Tomasson MH. Complete remission of TEL-PDGFRB-induced myeloproliferative disease in mice by receptor tyrosine kinase inhibitor SU11657. Blood. 2004;104:561–564
  28. Sohal J, Phan VT, Chan PV, et al. A model of APL with FLT3 mutation is responsive to retinoic acid and a receptor tyrosine kinase inhibitor, SU11657. Blood. 2003;101:3188–3197
  29. Backman U, Christofferson R. The selective class III/V receptor tyrosine kinase inhibitor SU11657 inhibits tumor growth and angiogenesis in experimental neuroblastomas grown in mice. Pediatr Res. 2005;57:690–695
  30. Kaspers GJL, Veerman AJP, Pieters R, et al. Mononuclear cells contaminating acute lymphoblastic leukaemic samples tested for cellular drug resistance using the methyl-thiazol-tetrazolium assay. Br J Cancer. 1994;70:1047–1052
  31. Klumper E, Pieters R, Kaspers GJL, et al. In vitro chemosensitivity assessed with the MTT assay in childhood acute non-lymphoblastic leukemia. Leukemia. 1995;9:1864–1869
  32. Goemans BF, Zwaan CM, Harlow A, et al. In vitro profiling of the sensitivity of pediatric leukemia cells to tipifarnib: identification of T-cell ALL and FAB M5 AML as the most sensitive subsets. Blood. 2005;106:3532–3537
  33. Cloos J, Goemans BF, Hess CJ, et al. Stability and prognostic influence of FLT3 mutations in paired initial and relapsed AML samples. Leukemia. 2006;20:1217–1220
  34. Kiyoi H, Towatari M, Yokota S, et al. Internal tandem duplication of the FLT3 gene is a novel modality of elongation mutation which causes constitutive activation of the product. Leukemia. 1998;12:1333–1337
  35. 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
  36. Knapper S, Mills KI, Gilkes 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
  37. Frohling S, Scholl C, Levine RL, et al. Identification of driver and passenger mutations of FLT3 by high-throughput DNA sequence analysis and functional assessment of candidate alleles. Cancer Cell. 2007;12:501–513
  38. Kim DW, Jo YS, Jung HS, et al. An orally administered multitarget tyrosine kinase inhibitor, SU11248, is a novel potent inhibitor of thyroid oncogenic RET/papillary thyroid cancer kinases. J Clin Endocrinol Metab. 2006;91:4070–4076
  39. de Bont ES, Fidler V, Meeuwsen T, et al. Vascular endothelial growth factor secretion is an independent prognostic factor for relapse-free survival in pediatric acute myeloid leukemia patients. Clin Cancer Res. 2002;8:2856–2861
  40. Hussong JW, Rodgers GM, Shami PJ. Evidence of increased angiogenesis in patients with acute myeloid leukemia. Blood. 2000;95:309–313
  41. Padro T, Ruiz S, Bieker R, et al. Increased angiogenesis in the bone marrow of patients with acute myeloid leukemia. Blood. 2000;95:2637–2644
  42. Deininger M. Resistance to imatinib: mechanisms and management. J Natl Compr Cancer Netw. 2005;3:757–768
  43. 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
  44. Faivre S, Delbaldo C, Vera K, et al. Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. J Clin Oncol. 2006;24:25–35
  45. Demetri GD, van Oosterom AT, Garrett CR, et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet. 2006;368:1329–1338
  46. Furukawa Y, Vu HA, Akutsu M, et al. Divergent cytotoxic effects of PKC412 in combination with conventional antileukemic agents in FLT3 mutation-positive versus -negative leukemia cell lines. Leukemia. 2007;21:1005–1014
  47. 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;104:1145–1150

PII: S0145-2126(10)00206-7

doi: 10.1016/j.leukres.2010.04.004

Leukemia Research
Volume 34, Issue 10 , Pages 1302-1307 , October 2010

Article Tools

* Image Usage & Resolution