Systemic mast cell disease (SMCD)

Identity

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.
Clinics	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 Name	KIT
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 ANLL-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 Name	SCF/MGF
Location	12q22
Dna / Rna	9 exons
Protein	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

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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.

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Longley BJ Jr, Morganroth GS, Tyrrell L, Ding TG, Anderson DM, Williams DE, Halaban R

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PMID 7682288

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.

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PMID 7479840

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

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PMID 8589724

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

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PMID 9029028

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

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PMID 9714703

Contributor(s)

Written	09-1998	Lidia Larizza, Alessandro Beghini
Updated	06-2000	Lidia Larizza, Alessandro Beghini

Citation

This paper should be referenced as such :

- . Systemic mast cell disease (SMCD). Atlas Genet Cytogenet Oncol Haematol. Septem ber 1998 . URL : http://AtlasGeneticsOncology.org/Genes/MastCellID2064.html

Larizza L, Beghini A . Systemic mast cell disease (SMCD). Atlas Genet Cytogenet Oncol Haematol. June 2000 . URL : http://AtlasGeneticsOncology.org/Genes/MastCellID2064.html

Larizza L, Beghini A . Systemic mast cell disease (SMCD). Atlas Genet Cytogenet Oncol Haematol. . URL : http://AtlasGeneticsOncology.org/Genes/MastCellID2064.html

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indexed on : Mon Aug 11 21:19:05 2008

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