Experimental Hematology
Volume 38, Issue 9 , Pages 744-755 , September 2010

In vitro and in vivo growth-inhibitory effects of cladribine on neoplastic mast cells exhibiting the imatinib-resistant KIT mutation D816V

  • Alexandra Böhm

      Affiliations

    • Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria
    • ,
  • Karoline Sonneck

      Affiliations

    • Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria
    • ,
  • Karoline V. Gleixner

      Affiliations

    • Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria
    • ,
  • Karina Schuch

      Affiliations

    • Institute of Immunology, Medical University of Vienna, Vienna, Austria
    • ,
  • Winfried F. Pickl

      Affiliations

    • Institute of Immunology, Medical University of Vienna, Vienna, Austria
    • ,
  • Katharina Blatt

      Affiliations

    • Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria
    • ,
  • Barbara Peter

      Affiliations

    • Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria
    • Department of Companion Animals and Horses, Clinic for Internal Medicine and Infectious Diseases, University of Veterinary Medicine Vienna, Vienna, Austria
    • ,
  • Harald Herrmann

      Affiliations

    • Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria
    • Ludwig Boltzmann Cluster Oncology, Vienna, Austria
    • ,
  • Gerit-Holger Schernthaner

      Affiliations

    • Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria
    • ,
  • Hubert Pehamberger

      Affiliations

    • Department of Dermatology, Medical University of Vienna, Vienna, Austria
    • Ludwig Boltzmann Cluster Oncology, Vienna, Austria
    • ,
  • Werner Rabitsch

      Affiliations

    • Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria
    • ,
  • Wolfgang R. Sperr

      Affiliations

    • Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria
    • ,
  • Peter Valent

      Affiliations

    • Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria
    • Ludwig Boltzmann Cluster Oncology, Vienna, Austria
    • Corresponding Author InformationOffprint requests to: Peter Valent, M.D., Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, AKH-Wien, Waehringer Guertel 18-20, A-1090 Vienna, Austria

Received 6 April 2010 ,Revised 13 May 2010 ,Accepted 18 May 2010.

References 

  1. Escribano L, Akin C, Castells M, Orfao A, Metcalfe DD. Mastocytosis: current concepts in diagnosis and treatment. Ann Hematol. 2002;81:677–690
  2. Valent P, Akin C, Sperr WR, et al. Diagnosis and treatment of systemic mastocytosis: state of the art. Br J Haematol. 2003;122:695–717
  3. Akin C, Metcalfe DD. Systemic mastocytosis. Annu Rev Med. 2004;55:419–432
  4. Metcalfe DD. Mast cells and mastocytosis. Blood. 2008;112:946–956
  5. Nagata H, Worobec AS, Oh CK, 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 U S A. 1995;92:10560–10564
  6. Longley BJ, Tyrrell L, Lu SZ, et al. Somatic c-kit activating mutation in urticaria pigmentosa and aggressive mastocytosis: establishment of clonality in a human mast cell neoplasm. Nat Genet. 1996;12:312–314
  7. Longley BJ, Metcalfe DD, Tharp M, et al. Activating and dominant inactivating c-kit catalytic domain mutations in distinct forms of human mastocytosis. Proc Natl Acad Sci U S A. 1999;96:1609–1614
  8. Fritsche-Polanz R, Jordan JH, Feix A, et al. Mutation analysis of C-KIT in patients with myelodysplastic syndromes without mastocytosis and cases of systemic mastocytosis. Br J Haematol. 2001;113:357–364
  9. Feger F, Ribadeau Dumas A, Leriche L, Valent P, Arock M. Kit and c-kit mutations in mastocytosis: a short overview with special reference to novel molecular and diagnostic concepts. Int Arch Allergy Immunol. 2002;127:110–114
  10. Garcia-Montero AC, Jara-Acevedo M, Teodosio C, et al. KIT mutation in mast cells and other bone marrow hematopoietic cell lineages in systemic mast cell disorders: a prospective study of the Spanish Network on Mastocytosis (REMA) in a series of 113 patients. Blood. 2006;108:2366–2372
  11. Valent P, Horny H-P, Escribano L, et al. Diagnostic criteria and classification of mastocytosis: a consensus proposal. Conference Report of “Year 2000 Working Conference on Mastocytosis.”. Leuk Res. 2001;25:603–625
  12. Valent P, Horny H-P, Li CY, et al. Mastocytosis (mast cell disease). In:  Jaffe ES,  Harris NL,  Stein H,  Vardiman JW editor. World Health Organization (WHO) Classification of Tumours. Pathology & Genetics. Tumours of Haematopoietic and Lymphoid Tissues. Vol. 1:Geneva, Switzerland: World Health Organization; 2001;p. 291–302
  13. Valent P, Akin C, Escribano L, et al. Standards and standardization in mastocytosis: consensus statements on diagnostics, treatment recommendations and response criteria. Eur J Clin Invest. 2007;37:435–453
  14. Horny HP, Akin C, Metcalfe DD, et al. Mastocytosis (mast cell disease). In:  Swerdlow SH,  Campo E,  Harris NL, et al. editor. World Health Organization (WHO) Classification of Tumours. Pathology & Genetics. Tumours of Haematopoietic and Lymphoid Tissues. Vol. 2:Geneva, Switzerland: World Health Organization; 2008;p. 54–63
  15. Sperr WR, Escribano L, Jordan JH, et al. Morphologic properties of neoplastic mast cells: delineation of stages of maturation and implication for cytological grading of mastocytosis. Leuk Res. 2001;25:529–536
  16. Lim KH, Tefferi A, Lasho TL, et al. Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. Blood. 2009;113:5727–5736
  17. Escribano L, Alvarez-Twose I, Sánchez-Muñoz L, et al. Prognosis in adult indolent systemic mastocytosis: a long-term study of the Spanish Network on Mastocytosis in a series of 145 patients. J Allergy Clin Immunol. 2009;124:514–521
  18. Valent P, Akin C, Sperr WR, et al. Aggressive systemic mastocytosis and related mast cell disorders: current treatment options and proposed response criteria. Leuk Res. 2003;27:635–641
  19. Valent P, Akin C, Sperr WR, et al. Mastocytosis: pathology, genetics, and current options for therapy. Leuk Lymphoma. 2005;46:35–48
  20. Valent P. Systemic mastocytosis. Cancer Treat Res. 2008;142:399–419
  21. Kluin-Nelemans HC, Jansen JH, Breukelman H, et al. Response to interferon alfa-2b in a patient with systemic mastocytosis. N Engl J Med. 1992;326:619–623
  22. Hauswirth AW, Simonitsch-Klupp I, Uffmann M, et al. Response to therapy with interferon alpha-2b and prednisolone in aggressive systemic mastocytosis: report of five cases and review of the literature. Leuk Res. 2004;28:249–257
  23. Quintas-Cardama A, Aribi A, Cortes J, Giles FJ, Kantarjian H, Verstovsek S. Novel approaches in the treatment of systemic mastocytosis. Cancer. 2006;107:1429–1439
  24. Tefferi A, Li CY, Butterfield JH, Hoagland HC. Treatment of systemic mast-cell disease with cladribine. N Engl J Med. 2001;344:307–309
  25. Escribano L, Pérez de Oteyza J, Núñez R, Orfao A. Cladribine induces immunophenotypical changes in bone marrow mast cells from mastocytosis. Report of a case of mastocytosis associated with a lymphoplasmacytic lymphoma. Leuk Res. 2002;26:1043–1046
  26. Kluin-Nelemans HC, Oldhoff JM, Van Doormaal JJ, et al. Cladribine therapy for systemic mastocytosis. Blood. 2003;102:4270–4276
  27. Pardanani A, Hoffbrand AV, Butterfield JH, Tefferi A. Treatment of systemic mast cell disease with 2-chlorodeoxyadenosine. Leuk Res. 2004;28:127–131
  28. Aichberger KJ, Sperr WR, Gleixner KV, Kretschmer A, Valent P. Treatment responses to cladribine and dasatinib in rapidly progressing aggressive mastocytosis. Eur J Clin Invest. 2008;38:869–873
  29. Droogendijk HJ, Kluin-Nelemans HJ, van Doormaal JJ, Oranje AP, van de Loosdrecht AA, van Daele PL. Imatinib mesylate in the treatment of systemic mastocytosis: a phase II trial. Cancer. 2006;107:345–351
  30. Gotlib J, Berubé C, Growney JD, et al. Activity of the tyrosine kinase inhibitor PKC412 in a patient with mast cell leukemia with the D816V KIT mutation. Blood. 2005;106:2865–2870
  31. Verstovsek S, Tefferi A, Cortes J, et al. Phase II study of dasatinib in Philadelphia chromosome-negative acute and chronic myeloid diseases, including systemic mastocytosis. Clin Cancer Res. 2008;14:3906–3915
  32. Ustun C, Corless CL, Savage N, et al. Chemotherapy and dasatinib induce long-term hematologic and molecular remission in systemic mastocytosis with acute myeloid leukemia with KIT D816V. Leuk Res. 2009;33:735–741
  33. Akin C, Brockow K, D'Ambrosio C, et al. Effects of tyrosine kinase inhibitor STI571 on human mast cells bearing wild-type or mutated forms of c-kit. Exp Hematol. 2003;31:686–692
  34. Ma Y, Zeng S, Metcalfe DD, et al. The c-KIT mutation causing human mastocytosis is resistant to STI571 and other KIT kinase inhibitors; kinases with enzymatic site mutations show different inhibitor sensitivity profiles than wild-type kinases and those with regulatory type mutations. Blood. 2002;99:1741–1744
  35. 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
  36. Butterfield JH, Weiler D, Dewald G, Gleich GJ. Establishment of an immature mast cell line from a patient with mast cell leukemia. Leuk Res. 1988;12:345–355
  37. Sillaber C, Strobl H, Bevec D, et al. IL-4 regulates c-kit proto-oncogene product expression in human mast and myeloid progenitor cells. J Immunol. 1991;147:4224–4228
  38. Gleixner KV, Mayerhofer M, Aichberger KJ, et al. PKC412 inhibits in vitro growth of neoplastic human mast cells expressing the D816V-mutated variant of KIT: comparison with AMN107, imatinib, and cladribine (2CdA) and evaluation of cooperative drug effects. Blood. 2006;107:752–759
  39. Van Cruchten S, Van Den Broeck W. Morphological and biochemical aspects of apoptosis, oncosis and necrosis. Anat Histol Embryol. 2002;31:214–223
  40. Zappulla JP, Dubreuil P, Desbois S, et al. Mastocytosis in mice expressing human Kit receptor with the activating Asp816Val mutation. J Exp Med. 2005;202:1635–1641
  41. Gotlib J. KIT mutations in mastocytosis and their potential as therapeutic targets. Immunol Allergy Clin North Am. 2006;26:575–592
  42. Schernthaner GH, Jordan JH, Ghannadan M, et al. Expression, epitope analysis, and functional role of the LFA-2 antigen detectable on neoplastic mast cells. Blood. 2001;98:3784–3792
  43. Nomura Y, Inanami O, Takahashi K, Matsuda A, Kuwabara M. 2-Chloro-2'-deoxyadenosine induces apoptosis through the Fas/Fas ligand pathway in human leukemia cell line MOLT-4. Leukemia. 2000;14:299–306
  44. Smal C, Lisart S, Ferrant A, Bontemps F, van den Neste E. Inhibition of the ERK pathway promotes apoptosis induced by 2-chloro-2'-deoxyadenosine in the B-cell leukemia cell line EHEB. Nucleosides Nucleotides Nucleic Acids. 2006;25:1009–1012
  45. Valent P, Akin C, Sperr WR, Horny HP, Metcalfe DD. Smouldering mastocytosis: a novel subtype of systemic mastocytosis with slow progression. Int Arch Allergy Immunol. 2002;127:137–139
  46. Dighiero G. Adverse and beneficial immunological effects of purine nucleoside analogues. Hematol Cell Ther. 1996;38(Suppl 2):S75–S81
  47. Rossini MS, de Souza EM, Cintra ML, Pagnano KB, Chiari AC, Lorand-Metze I. Cutaneous adverse reaction to 2-chlorodeoxyadenosine with histological flame figures in patients with chronic lymphocytic leukaemia. J Eur Acad Dermatol Venereol. 2004;18:538–542
  48. Grey MR, Flanagan NG, Kelsey PR. Severe skin rash in two consecutive patients treated with 2-chlorodeoxyadenosine for hairy cell leukaemia at a single institution. Clin Lab Haematol. 2000;22:111–113

PII: S0301-472X(10)00202-X

doi: 10.1016/j.exphem.2010.05.006

Experimental Hematology
Volume 38, Issue 9 , Pages 744-755 , September 2010

Article Tools

* Image Usage & Resolution