• 1
    Molderings GJ, Brettner S, Homann J, Afrin LB. Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options. J Hematol Oncol 2011; 4:10.
  • 2
    Akin C, Valent P, Metcalfe DD. Mast cell activation syndrome: proposed diagnostic criteria. J Allergy Clin Immunol 2010; 126:1099104.
  • 3
    Valent P, Akin C, Arock M et al. Definitions, Criteria and Global Classification of Mast Cell Disorders with Special Reference to Mast Cell Activation Syndromes: a Consensus Proposal. Int Arch Allergy Immunol 2012; 157:21525.
  • 4
    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; 37:43553.
  • 5
    Alvarez-Twose I, González de Olano D, Sánchez-Muñoz L etal. Clinical, biological, and molecular characteristics of clonal mast cell disorders presenting with systemic mast cell activation symptoms. J Allergy Clin Immunol 2010; 125:126978.
  • 6
    Hamilton MJ, Hornick JL, Akin C, Castells MC, Greenberger NJ. Mast cell activation syndrome: a newly recognized disorder with systemic clinical manifestations. J Allergy Clin Immunol 2011; 128:14752.
  • 7
    Hermine O, Lortholary O, Leventhal PS et al. Case–control cohort study of patients' perceptions of disability in mastocytosis. PLoS One 2008; 3:e2266.
  • 8
    Lanternier F, Cohen-Akenine A, Palmerini F et al. Phenotypic and genotypic characteristics of mastocytosis according to the age of onset. PLoS One 2008; 3:e1906.
  • 9
    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; 124:51421.
  • 10
    Alvarez-Twose I, González-de-Olano D, Sánchez-Muñoz L et al. Validation of the REMA Score for Predicting Mast Cell Clonality and Systemic Mastocytosis in Patients with Systemic Mast Cell Activation Symptoms. Int Arch Allergy Immunol 2011; 157:27580.
  • 11
    Merante S, Magliacane D, Neri I et al. The New Italian Mastocytosis Registry. 53rd ASH Annual Meeting and Exposition 2010; Poster 3805, []
  • 12
    Lim KH, Tefferi A, Lasho TL et al. Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. Blood 2009; 113:572736.
  • 13
    Lucas HJ, Brauch CM, Settas L, Theoharides TC. Fibromyalgia – new concepts of pathogenesis and treatment. Int J Immunopathol Pharmacol 2006; 19:59.
  • 14
    Frieling T, Meis K, Kolck UW et al. Evidence for mast cell activation in patients with therapy-resistant irritable bowel syndrome. Z Gastroenterol 2011; 49:1914.
  • 15
    Longley BJ, Metcalfe DD, Tharp M, Wang X, Tyrrell L, Lu SZ, Heitjan D, Ma Y. Activating and dominant inactivating c-kit catalytic domain mutations in distinct clinical forms of human mastocytosis. Proc Natl Acad Sci U S A 1999; 96:160914.
  • 16
    Rosbotham JL, Malik NM, Syrris P et al. Lack of c-kit mutation in familial urticaria pigmentosa. Br J Dermatol 1999; 140:84952.
  • 17
    Tang X, Boxer M, Drummond A, Ogston P, Hodgins M, Burden AD. A germline mutation in KIT in familial diffuse cutaneous mastocytosis. J Med Genet 2004; 41:e88.
  • 18
    Bodemer C, Hermine O, Palmérini F et al. Pediatric mastocytosis is a clonal disease associated with D(816)V and other activating c-KIT mutations. J Invest Dermatol 2010; 130:80415.
  • 19
    Foster R, Byrnes E, Meldrum C et al. Association of paediatric mastocytosis with a polymorphism resulting in an amino acid substitution (M541L) in the transmembrane domain of c-KIT. Br J Dermatol 2008; 159:11609.
  • 20
    Wasag B, Niedoszytko M, Piskorz A et al. Novel activating KIT-N822I mutation in familial cutaneous mastocytosis. Exp Hematol 2011; 39:85965.
  • 21
    Noack F, Escribano L, Sotlar K, Nunez R, Schuetze K, Valent P, Horny HP. Evolution of urticaria pigmentosa into indolent systemic mastocytosis: abnormal immunophenotype of mast cells without evidence of c-Kit mutation ASP-816-VAL. Leuk Lymphoma 2003; 44:3139.
  • 22
    Vogel NM, Lichtin AE, Hsieh FH. Longitudinal disease progression in mastocytosis syndromes: a retrospective chart review. J Allergy Clin Immunol 2006; 117(Suppl):S125.
  • 23
    Uzzaman A, Maric I, Noel P, Kettelhut BV, Metcalfe DD, Carter MC. Pediatric-onset mastocytosis: a long term clinical follow-up and correlation with bone marrow histopathology. Pediatr Blood Cancer 2009; 53:62934.
  • 24
    Bhamidimarri K, Sidhu L, Xie J, Pulakhandam U, Gumstae V. Gastrointestinal manifestations in cutaneous mastocytosis evolving into systemic mastocytosis. Am J Gastroenterol 2010; 105(Suppl. 1):S348.
  • 25
    Molderings GJ, Kolck UW, Scheurlen C, Brüss M, Homann J, von Kügelgen I. Multiple novel alterations in Kit tyrosine kinase in patients with gastrointestinally pronounced systemic mast cell activation disorder. Scand J Gastroenterol 2007; 42:104553.
  • 26
    Molderings GJ, Meis K, Kolck UW, Homann J, Frieling T. Comparative analysis of mutation of tyrosine kinase kit in mast cells from patients with systemic mast cell activation syndrome and healthy subjects. Immunogenetics 2010; 62:7217.
  • 27
    Orfao A, Garcia-Montero AC, Sanchez L, Escribano L; REMA. Recent advances in the understanding of mastocytosis: the role of KIT mutations. Br J Haematol 2007; 138:1230.
  • 28
    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; 108:236672.
  • 29
    Kristensen T, Broesby-Olsen S, Vestergaard H, Bindslev-Jensen C, Møller MB; on behalf of the Mastocytosis Centre Odense University Hospital (MastOUH). Circulating KIT D816V mutation-positive non-mast cells in peripheral blood are characteristic of indolent systemic mastocytosis. Eur J Haematol 2012; 89:426.
  • 30
    Kohno M, Yamasaki S, Tybolewicz VLJ, Saito T. Rapid and large amount of autocrine IL-3 production is responsible for mast cell survival by IgE in the absence of antigen. Blood 2005; 105:205965.
  • 31
    Aichberger KJ, Gleixner KV, Mirkina I et al. Identification of proapoptotic Bim as a tumor suppressor in neoplastic mast cells: role of KIT D816V and effects of various targeted drugs. Blood 2009; 114:534251.
  • 32
    Rottem M, Okada T, Goff JP, Metcalfe DD. Mast cells cultured from the peripheral blood of normal donors and patients with mastocytosis originate from a CD34+/FcεRI-cell population. Blood 1994; 84:248996.
  • 33
    Jordan JH, Jäger E, Sperr WR et al. Numbers of colony-forming progenitors in patients with systemic mastocytosis: potential diagnostic implications and comparison with myeloproliferative disorders. Eur J Clin Invest 2003; 33:6118.
  • 34
    Ning ZQ, Li J, Arceci RJ. Signal transducer and activator of transcription 3 activation is required for Asp816 mutant c-kit-mediated cytokine-independent survival and proliferation in human leukemia cells. Blood 2001; 97:355967.
  • 35
    Yang Y, Li L, Wong GW, Krilis SA, Madhusudhan MS, Sali A, Stevens RL. RasGRP4, a new mast cell-restricted Ras guanine nucleotide-releasing protein with calcium- and diacylglycerol-binding motifs. Identification of defective variants of this signaling protein in asthma, mastocytosis, and mast cell leukemia patients and demonstration of the importance of RasGRP4 in mast cell development and function. J Biol Chem 2002; 277:2575674.
  • 36
    Roskoski R. Structure and regulation of Kit protein-tyrosine kinase – the stem cell factor receptor. Bichem Biophys Res Commun 2005; 338:130715.
  • 37
    Roskoski R. Signaling by Kit protein-tyrosine kinase – the stem cell factor receptor. Biochem Biophys Res Commun 2005; 337:113.
  • 38
    Bougherara H, Subra F, Crépin R, Tauc P, Auclair C, Poul MA. The aberrant localization of oncogenic kit tyrosine kinase receptor mutants is reversed on specific inhibitory treatment. Mol Cancer Res 2009; 7:152533.
  • 39
    Toffalini F, Demoulin JB. New insights into the mechanisms of hematopoietic cell transformation by activated receptor tyrosine kinases. Blood 2010; 116:242937.
  • 40
    Gilfillan AM, Rivera J. The tyrosine kinase network regulating mast cell activation. Immunol Rev 2009; 228:14969.
  • 41
    Breuer C, Oh J, Molderings GJ, Schemann M, Kuch B, Mayatepek E, Adam R. Therapy-refractory gastrointestinal motility disorder in a child with c-kit mutations. World J Gastroenterol 2010; 16:43636.
  • 42
    Hayashi S, Kunisada T, Ogawa M, Yamaguchi K, Nishikawa S. Exon skipping by mutation of an authentic splice site of c-kit gene in W/W mouse. Nucleic Acids Res 1991; 19:126771.
  • 43
    Caruana G, Cambareri AC, Ashman LK. Isoforms of c-KIT differ in activation of signalling pathways and transformation of NIH3T3 fibroblasts. Oncogen 1999; 18:557381.
  • 44
    Voytyuk O, Lennartsson J, Mogi A, Caruana G, Courtneidge S, Ashman LK, Rönnstrand L. Src family kinases are involved in the differential signaling from two splice forms of c-Kit. J Biol Chem 2003; 278:915966.
  • 45
    Crosier PS, Ricciardi ST, Hall LR, Vitas MR, Clark SC, Crosier KE. Expression of isoforms of the human receptor tyrosine kinase c-kit in leukemic cell lines and acute myeloid leukemia. Blood 1993; 82:11518.
  • 46
    Mayerhofer M, Gleixner KV, Hoelbl A et al. Unique effects of KIT D816V in BaF3 cells: induction of cluster formation, histamine synthesis, and early mast cell differentiation antigens. J Immunol 2008; 180:546676.
  • 47
    Yang Y, Létard S, Borge L. Pediatric mastocytosis-associated KIT extracellular domain mutations exhibit different functional and signaling properties compared with KIT-phosphotransferase domain mutations. Blood 2010; 116:111423.
  • 48
    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; 106:286570.
  • 49
    Fritsche-Polanz R, Fritz M, Huber A, Sotlar K, Sperr WR, Mannhalter C, Födinger M, Valent P. High frequency of concomitant mastocytosis in patients with acute myeloid leukemia exhibiting the transforming KIT mutation D816V. Mol Oncol 2010; 4:33546.
  • 50
    Sotlar K, Colak S, Bache A, Berezowska S, Krokowski M, Bültmann B, Valent P, Horny HP. Variable presence of KIT(D816V) in clonal haematological non-mast cell lineage diseases associated with systemic mastocytosis (SM-AHNMD). J Pathol 2010; 220:58695.
  • 51
    Akin C, Kirshenbaum AS, Semere T, Worobec AS, Scott LM, Metcalfe DD. Analysis of the surface expression of c- kit Asp816Val activating mutation in T cells, B cells, and myelomonocytic cells in patients with mastocytosis. Exp Hematol 2000; 28:1407.
  • 52
    Nedoszytko B, Niedoszytko M, Lange M et al. Interleukin-13 promoter gene polymorphism –1112C/T is associated with the systemic form of mastocytosis. Allergy 2009; 64:28794.
  • 53
    Kaur D, Hollins F, Woodman L, Yang W, Monk P, May R, Bradding P, Brightling CE. Mast cells express IL-13Rα1: IL-13 promotes human lung mast cell proliferation and FcεRI expression. Allergy 2006; 61:104753.
  • 54
    Daley T, Metcalfe DD, Akin C. Association of the Q576R polymorphism in the interleukin-4 receptor α chain with indolent mastocytosis limited to the skin. Blood 2001; 98:8802.
  • 55
    Bailey DP, Kashyap M, Mirmonsef P, Bouton LA, Domen J, Zhu J, Dessypris EN, Ryan JJ. Interleukin-4 elicits apoptosis of developing mast cells via a Stat6-dependent mitochondrial pathway. Exp Hematol 2004; 32:529.
  • 56
    D'Ambrosio C, Akin C, Wu Y, Magnusson MK, Metcalfe DD. Gene expression analysis in mastocytosis reveals a highly consistent profile with candidate molecular markers. J Allergy Clin Immunol 2003; 112:116270.
  • 57
    Swolin B, Rödjer S, Roupe G. Cytogenetic Studies in Patients with Mastocytosis. Cancer Genet Cytogenet 2000; 120:1315.
  • 58
    Swolin B, Rödjer S, Ogärd I, Roupe G. Trisomies 8 and 9 not detected with fish in patients with mastocytosis. Am J Hematol 2002; 70:3245.
  • 59
    Jost E, Michaux L, van den Abeele M et al. Complex karyotype and absence of mutation in the c-Kit receptor in aggressive mastocytosis presenting with pelvic osteolysis, eosinophilia and brain damage. Ann Hematol 2001; 80:3027.
  • 60
    Offidani A, Cellini A, Simonetti O, Bossi G. Urticaria pigmentosa in monozygotic twins. Arch Dermatol 1994; 130:9356.
  • 61
    Pec J, Palencarova E, Malisova S, Dobrota D, Hajtman A, Pec M, Lepej J. Urticaria pigmentosa in identical male twins. Acta Derm Venereol 1995; 75:244.
  • 62
    Nishida T, Hirota S, Taniguchi M et al. Familial gastrointestinal stromal tumours with germline mutation of the KIT gene. Nat Genet 1998; 19:3234.
  • 63
    Trevisan G, Pauluzzi P, Gatti A, Semeraro A. Familial mastocytosis associated with neurosensory deafness. J Eur Acad Dermatol Venereol 2000; 14:11922.
  • 64
    Beghini A, Tibiletti MG, Roversi G, Chiaravalli AM, Serio G, Capella C, Larizza L. Germline mutation in the juxtamembrane domain of the kit gene in a family with gastrointestinal stromal tumors and urticaria pigmentosa. Cancer 2001; 92:65762.
  • 65
    Ben-Amitai D, Metzker A, Cohen HA. Pediatric cutaneous mastocytosis: a review of 180 patients. Isr Med Assoc J 2005; 7:3202.
  • 66
    Yanagihori H, Oyama N, Nakamura K, Kaneko F. C-kit mutations in patients with childhood-onset mastocytosis and genotype–phenotype correlation. J Mol Diagn 2005; 7:2527.
  • 67
    de la Sotta PD, Romero WA, Kramer D, Cárdenas C, González S. Cutaneous mastocytosis in twins: multiple mastocytomas and urticaria pigmentosa in two pairs of monozygotic twins. Pediatr Dermatol 2011; 28:5857.
  • 68
    Zhang LY, Smith ML, Schultheis B, Fitzgibbon J, Lister TA, Melo JV, Cross NCP, Cavenagh JD. A novel K5091 mutation of KIT identified in familial mastocytosis – in vitro and in vivo responsiveness to imatinib therapy. Leuk Res 2006; 30:3738.
  • 69
    Hartmann K, Wardelmann E, Ma Y et al. Novel germline mutation of KIT associated with familial gastrointestinal stromal tumors and mastocytosis. Gastroenterology 2005; 129:10426.
  • 70
    Burks KD, Wenzel SE, Jones SM. Familial cases of mast cell diseases[abstract]. J Invest Med 2005; 53:S300.
  • 71
    Bursztejn AC, Bronner M, Kanny G, Barbaud A, Morisset M, Jonveaux P. Genetic evaluation of familial mastocytosis[abstract]. J Invest Dermatol 2009; 129:2528.
  • 72
    Verzijl A, Heide R, Oranje AP, van Schaik RHN. c-Kit Asp-816-Val mutation analysis in patients with mastocytosis. Dermatology 2007; 214:1520.
  • 73
    Welle MM, Bley CR, Howard J, Rüfenacht S. Canine mast cell tumours: a review of the pathogenesis, clinical features, pathology and treatment. Vet Dermatol 2008; 19:32139.
  • 74
    O'Brien S, Tefferi A, Valent P. Chronic myelogenous leukemia and myeloproliferative disease. Hematology Am Soc Hematol Educ Program 2004; 14662.
  • 75
    Buttner C, Henz BM, Welker P, Sepp NT, Grabbe J. Identification of activating c-kit mutations in adult-, but not in childhood-onset indolent mastocytosis: a possible explanation for divergent clinical behavior. J Invest Dermatol 1998; 111:122731.
  • 76
    Sotlar K, Horny HP, Simonitsch I et al. CD25 indicates the neoplastic phenotype of mast cells: a novel immunohistochemical marker for the diagnosis of systemic mastocytosis (SM) in routinely processed bone marrow biopsy specimens. Am J Surg Pathol 2004; 28:131925.
  • 77
    Pignon JM, Giraudier S, Duquesnoy P, Jouault H, Imbert M, Vainchenker W, Vernant JP, Tulliez M. A new c-kit mutation in a case of aggressive mast cell disease. Br J Haematol 1997; 96:3746.
  • 78
    Baek JO, Kang HK, Na SY, Lee JR, Roh JY, Lee JH, Kim HJ, Park S. N822K c-kit mutation in CD30-positive cutaneous pleomorphic mastocytosis after germ cell tumour of the ovary. Br J Dermatol 2012; 166:13703.
  • 79
    Galderisi CD, Corless CL, Wolford J, Harrell T, Heinrich MC, Press RD. Simultaneous JAK2 V617F and KIT D816V mutations in systemic mastocytosis. Mod Pathol 2006; 19:225A6A.
  • 80
    Steensma DP, Dewald GW, Lasho TL, Powell HL, McClure RF, Levine RL, Gilliland DG, Tefferi A. The JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both “atypical” myeloproliferative disorders and myelodysplastic syndromes. Blood 2005; 106:12079.
  • 81
    Cools J, DeAngelo DJ, Gotlib J et al. A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med 2003; 348:120114.
  • 82
    Pardanani A, Ketterling RP, Brockman SR et al. CHIC2 deletion, a surrogate for FIP1L1–PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate therapy. Blood 2003; 102:30936.
  • 83
    Robyn J, Lemery S, McCoy JP et al. Multilineage involvement of the fusion gene in patients with FIP1L1/PDGFRA-positive hypereosinophilic syndrome. Br J Haematol 2006; 132:28692.
  • 84
    Gotlib J, Cross NCR, Gilliland DG. Eosinophilic disorders: molecular pathogenesis, new classification, and modern therapy. Best Pract Res Clin Haematol 2006; 19:53569.
  • 85
    Wilson TM, Maric I, Simakova O et al. Clonal analysis of NRAS activating mutations in KIT-D816V systemic mastocytosis. Haematologica 2011; 96:45963.
  • 86
    Bandi SR, Brandts C, Rensinghoff M et al. E3 ligase-defective Cbl mutants lead to a generalized mastocytosis and a myeloproliferative disease. Blood 2009; 114:4197208.
  • 87
    van Rijn RM, van Marle A, Chazot PL et al. Cloning and characterization of dominant negative splice variants of the human histamine H4 receptor. Biochem J 2008; 414:12131.
  • 88
    Tefferi A, Levine RL, Lim KH et al. Frequent TET2 mutations in systemic mastocytosis: clinical, KITD816V and FIP1L1–PDGFRA correlates. Leukemia 2009; 23:9004.
  • 89
    Schroer BC, Han YC, Hsieh FH. Identification of TET2 mutations in subjects with systemic mastocytosis and hypereosinophilic syndrome[abstract]. J Allergy Clin Immunol 2010; 125:AB232.
  • 90
    Nedoszytko B, Niedoszytko M, Lange M et al. Associations of TNF-α gene polymorphisms and mastocytosis. A study of the European Competence Network in Mastocytosis (ECNM)[abstract]. Allergy 2008; 63(Suppl. 88):154.
  • 91
    Niedoszytko M, Nedoszytko B, Lange M et al. Vascular Endothelial Growth Factor (VEGF) promoter gene polymorphism in mastocytosis. A study of the European Competence Network on Mastocytosis (ECNM)[abstract]. Allergy 2008; 63(Suppl. 88):322.
  • 92
    Alfter K, von Kügelgen I, Haenisch B et al. New aspects of liver abnormalities as part of the systemic mast cell activation syndrome. Liver Int 2009; 29:1816.