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Systemic mast cell disease (SMCD)

Written2000-06Lidia Larizza, Alessandro Beghini
Medical Genetics, San Paolo School of Medicine, University of Milan Via A. di Rudini, 8, 20142 Milano, Italy
This article is an update of :
1998-09Lidia Larizza, Alessandro Beghini
Medical Genetics, San Paolo School of Medicine, University of Milan Via A. di Rudini, 8, 20142 Milano, Italy

(Note : for Links provided by Atlas : click)


ICD-Morpho 9741/3 Systemic mastocytosis
ICD-Morpho 9742/3 Mast cell leukaemia
ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
Atlas_Id 2064
Note mastocytosis is a heterogeneous clinical entity which is classified into four categories:
1- indolent mastocytosis (the most common form),
2- mastocytosis with an associated hematologic disorder,
3- mast cell leukemia and
4- aggressive mastocytosis

Clinics and Pathology

Phenotype / cell stem origin mast cell
Etiology involvement of KIT/SCF has been demonstrated in a few cases, but the diversity of the clinical pattern has not yet been elucidated;increased soluble SCF has been reported in the skin of patient with indolent mastocytosis; c-KIT mutations have been identified in patients with all forms of sporadic mastocytosis.
  • indolent mastocytosis involves the skin, bone marrow and gastrointestinal tract; clinical features range from a single cutaneous nodule to multiple pigmented macules resulting from increased epidermal melanin and papules (urticaria pigmentosa) or diffuse cutaneous involvement; bullae, vescicles and abnormal telangiectasia may be seen; gastrointestinal involvement leads to symptoms such as nausea, vomiting and abdominal pain.
  • in mastocytosis with an associated hematological disorder the urticaria pigmentosa symptoms are accompanied by a variety of haematological findings due to mast cell infiltrates to bone marrow, spleen, liver and lymph nodes.
  • mast cell leukemia is characterized by proliferation and infiltration of immature mast cells in bone marrow, peripheral blood and various extramedullary tissues.
  • aggressive mastocytosis is characterized by aggressive involvement of several haematopoietic organs
  • Pathology accumulation of mast cells in various organs and release of mast cell mediators which are responsible for the different clinical signs
    Prognosis highly dependent on the form being severe, often fatal, in all types with the exception of the indolent form

    Genes involved and Proteins

    Gene NameKIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog)
    Location 4q12
    Note All mutations with the exception of Gly560Val cluster to c-kit exon 17. Direct or indirect evidence has been provided that mutations affecting codon 816 promote ligand-independent autophosphorylation of the mutant receptor
    Dna / Rna 21 exons
    Protein transmembrane SCF/MGF receptor with tyrosine kinase activity; binding of ligand (SCF) induces receptor dimerization, autophosphorylation and signal transduction via molecules containing SH2- domains
    Somatic mutations (see diagram) Gly560Val, Asp816Val, Asp816Tyr, Asp820Gly
  • Asp816Val in peripheral blood lymphocytes (mastocytosis with an associated hematological disorder: AHD)
  • Asp816Val in skin and spleen mast cells from patients with aggressive mastocytosis
  • Asp816Tyr in blasts from a patient with AML-M2 with mast cell involvement
  • Asp820 Gly in blasts from a patient with aggressive SMCD
  • Asp816Val and Gly560Val have been found in a human mast cell leukemia cell line (HMC1)
  • Gene NameKITLG (KIT ligand)
    Location 12q21.32
    Dna / Rna 9 exons
  • soluble SCF : 248 aminoacids containing a proteolytic cleavage site encoded by exon 6 sequences, which is processed, giving rise to an active form (soluble) of 165 aminoacids; membrane-bound SCF : 220 aminoacids, results from alternative splicing of exon 6
  • Note: increased soluble SCF has been detected in the skin of patients with indolent mastocytosis; SCF-specific transcripts are detected by in situ RT-PCR in mast cell infiltrates in papulae from mastocytosis patients
  • Bibliography

    In vivo differentiation of mast cells from acute myeloid leukemia blasts carrying a novel activating ligand-independent C-kit mutation.
    Beghini A, Cairoli R, Morra E, Larizza L
    Blood cells, molecules & diseases. 1998 ; 24 (2) : 262-270.
    PMID 9714703
    Identification of mutations in the coding sequence of the proto-oncogene c-kit in a human mast cell leukemia cell line causing ligand-independent activation of c-kit product.
    Furitsu T, Tsujimura T, Tono T, Ikeda H, Kitayama H, Koshimizu U, Sugahara H, Butterfield JH, Ashman LK, Kanayama Y
    The Journal of clinical investigation. 1993 ; 92 (4) : 1736-1744.
    PMID 7691885
    Altered metabolism of mast-cell growth factor (c-kit ligand) in cutaneous mastocytosis.
    Longley BJ Jr, Morganroth GS, Tyrrell L, Ding TG, Anderson DM, Williams DE, Halaban R
    The New England journal of medicine. 1993 ; 328 (18) : 1302-1307.
    PMID 7682288
    Somatic c-KIT activating mutation in urticaria pigmentosa and aggressive mastocytosis: establishment of clonality in a human mast cell neoplasm.
    Longley BJ, Tyrrell L, Lu SZ, Ma YS, Langley K, Ding TG, Duffy T, Jacobs P, Tang LH, Modlin I
    Nature genetics. 1996 ; 12 (3) : 312-314.
    PMID 8589724
    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.
    Nagata H, Worobec AS, Oh CK, Chowdhury BA, Tannenbaum S, Suzuki Y, Metcalfe DD
    Proceedings of the National Academy of Sciences of the United States of America. 1995 ; 92 (23) : 10560-10564.
    PMID 7479840
    A new c-kit mutation in a case of aggressive mast cell disease.
    Pignon JM, Giraudier S, Duquesnoy P, Jouault H, Imbert M, Vainchenker W, Vernant JP, Tulliez M
    British journal of haematology. 1997 ; 96 (2) : 374-376.
    PMID 9029028
    Bcl10 can promote survival of antigen-stimulated B lymphocytes.
    Tian MT, Gonzalez G, Scheer B, DeFranco AL
    Blood. 2005 ; 106 (6) : 2105-2112.
    PMID 15878976


    This paper should be referenced as such :
    Larizza, L ; Beghini, A
    Systemic mast cell disease (SMCD)
    Atlas Genet Cytogenet Oncol Haematol. 2000;4(3):125-126.
    Free journal version : [ pdf ]   [ DOI ]
    On line version :
    History of this paper:
    Larizza, L ; Beghini, A. Systemic mast cell disease (SMCD). Atlas Genet Cytogenet Oncol Haematol. 1999;3(1):19-20.

    Other genes implicated (Data extracted from papers in the Atlas) [ 4 ]


    External links

    COSMICHisto = - Site = haematopoietic_and_lymphoid_tissue (COSMIC)
    arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9741/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
    arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9742/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
    arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9861/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
    REVIEW articlesautomatic search in PubMed
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