Leukemia Research
Volume 33, Issue 5 , Pages 735-741 , May 2009

Chemotherapy and dasatinib induce long-term hematologic and molecular remission in systemic mastocytosis with acute myeloid leukemia with KITD816V

  • Celalettin Ustun

      Affiliations

    • Medical College of Georgia, Department of Medicine, Section of Hematology/Oncology, Augusta, GA, USA
    • Corresponding Author InformationCorresponding author at: Medical College of Georgia, Department of Medicine, Section of Hematology/Oncology, 1120 15th Street, BAA-5407 Augusta, GA 30912-3125, United States. Tel.: +1 706 721 2505; fax: +1 706 721 8302.
    • ,
  • Christopher L. Corless

      Affiliations

    • Oregon Health & Science University Cancer Institute, Portland, OR, USA
    • ,
  • Natasha Savage

      Affiliations

    • Department of Pathology, Augusta, GA, USA
    • ,
  • Warren Fiskus

      Affiliations

    • Cancer Center, Augusta, GA, USA
    • ,
  • Elizabeth Manaloor

      Affiliations

    • Department of Pathology, Augusta, GA, USA
    • ,
  • Michael C. Heinrich

      Affiliations

    • Oregon Health & Science University Cancer Institute, Portland, OR, USA
    • ,
  • Grant Lewis

      Affiliations

    • Medical College of Georgia, Department of Medicine, Section of Hematology/Oncology, Augusta, GA, USA
    • ,
  • Preetha Ramalingam

      Affiliations

    • Department of Pathology, Augusta, GA, USA
    • ,
  • Ilana Kepten

      Affiliations

    • Oregon Health & Science University Cancer Institute, Portland, OR, USA
    • ,
  • Anand Jillella

      Affiliations

    • Medical College of Georgia, Department of Medicine, Section of Hematology/Oncology, Augusta, GA, USA
    • ,
  • Kapil Bhalla

      Affiliations

    • Medical College of Georgia, Department of Medicine, Section of Hematology/Oncology, Augusta, GA, USA
    • Cancer Center, Augusta, GA, USA

Received 13 June 2008 ,Revised 22 September 2008 ,Accepted 24 September 2008.

References 

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  2. Sperr WR, Horny HP, Valent P. Spectrum of associated clonal hematologic non-mast cell lineage disorders occurring in patients with systemic mastocytosis. Int Arch Allergy Immunol. 2002;127:140–142
  3. Foster R, Griffith R, Ferrao P, Ashman L. Molecular basis of the constitutive activity and STI571 resistance of Asp816Val mutant KIT receptor tyrosine kinase. J Mol Graph Model. 2004;23:139–152
  4. Nagata H, Worobec AS, Oh CK, Chowdhury BA, Tannenbaum S, Suzuki Y, et al. Identification of a point mutation in the catalytic domain of the protooncogene c-KIT in peripheral blood mononuclear cells of patients who have mastocytosis with an associated hematologic disorder. Proc Natl Acad Sci USA. 1995;92:10560–10564
  5. Frost MJ, Ferrao PT, Hughes TP, Ashman LK. Juxtamembrane mutant V560GKit is more sensitive to Imatinib (STI571) compared with wild-type c-KIT whereas the kinase domain mutant D816VKit is resistant. Mol Cancer Ther. 2002;1:1115–1124
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  7. Shah NP, Lee FY, Luo R, Jiang Y, Donker M, Akin C. Dasatinib (BMS-354825) inhibits KITD816V, an imatinib-resistant activating mutation that triggers neoplastic growth in most patients with systemic mastocytosis. Blood. 2006;108:286–291
  8. Schittenhelm MM, Shiraga S, Schroeder A, Corbin AS, Griffith D, Lee FY, et al. Dasatinib (BMS-354825), a dual SRC/ABL kinase inhibitor, inhibits the kinase activity of wild-type, juxtamembrane, and activation loop mutant KIT isoforms associated with human malignancies. Cancer Res. 2006;66:473–481
  9. Verstovsek S, Ayalew T, Jorge C, O’Brien S, Garcia-Monero G, Pardani A, et al. Phase II Study of Dasatinib (SPRYCELTM) in Philadelphia chromosome-negative acute and chronic myeloid diseases, including systemic mastocytosis [Abstract]. Blood. 2007;110:1039a;[Abstract 3551]
  10. Pullarkat VA, Bueso-Ramos C, Lai R, Kroft S, Wilson CS, Pullarkat ST, et al. Systemic mastocytosis with associated clonal hematological non-mast-cell lineage disease: analysis of clinicopathologic features and activating c-KIT mutations. Am J Hematol. 2003;73:12–17
  11. Pullarkat V, Bedell V, Kim Y, Bhatia R, Nakamura R, Forman S, et al. Neoplastic mast cells in systemic mastocytosis associated with t(8;21) acute myeloid leukemia are derived from the leukemic clone. Leuk Res. 2007;31:261–265
  12. Nagai S, Ichikawa M, Takahashi T, Sato H, Yokota H, Oshima K, et al. The origin of neoplastic mast cells in systemic mastocytosis with AML1/ETO-positive acute myeloid leukaemia. Exp Hematol. 2007;35:1747–1752
  13. Wong KF, Chan JK, Chan JC, Kwong YL, Ma SK, Chow TC. Concurrent acute myeloid leukemia and systemic mastocytosis. Am J Hematol. 1991;38:243–244
  14. Bernd HW, Sotlar K, Lorenzen J, Osieka R, Fabry U, Valent P, et al. Acute myeloid leukaemia with t(8;21) associated with “occult” mastocytosis. Report of an unusual case and review of the literature. J Clin Pathol. 2004;57:324–328
  15. Rondoni M, Paolini S, Colarossi S, Piccaluga PP, Papayannidis C, Palandiri F, et al. Response to dasatinib in patients with aggressive systemic mastocytosis with D816V Kit Mutation [Abstract]. Blood. 2007;110:1042a;[Abstract 3562]
  16. Purtill D, Sinniah R, Cooney J, Carnley B, Cull G, Augustson B, et al. Dasatinib therapy for systemic mastocytosis: four cases. Eur J Haem. 2008;80:456–458
  17. Benz R, Boesiger J, Fehr J. Systemic mastocytosis with c-KITD816V mutation treated with dasatinib (abstract(. Blood. 2007;110:258b;[Abstract 4656]
  18. Gleixner KV, Mayerhofer M, Rix U, Hoermann G, Gruze A, Krauth MT, et al. Delineation of a KIT-Independent oncogenic pathway in neoplastic mast cells that involves Lyn and Btk, and can be disrupted by the KIT/Lyn/Btk-Targeting drug (abstract(. Blood. 2007;110:460a;[Abstract 1541]
  19. Gotlib J. KIT mutations in mastocytosis and their potential as therapeutic targets. Immunol Allergy Clin North Am. 2006;26:575–592
  20. Metcalfe DD. Regulation of normal and neoplastic human mast cell development in mastocytosis. Trans Am Clin Climatol Assoc. 2005;116:185–203

PII: S0145-2126(08)00452-9

doi: 10.1016/j.leukres.2008.09.027

Leukemia Research
Volume 33, Issue 5 , Pages 735-741 , May 2009

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