Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10721 (c-kit)
 6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The term mastocytosis covers a heterogeneous group of disorders characterized by the abnormal growth and accumulation of MCs in one or more organ systems. Clinical symptoms occur from the release of chemical mediators or pathologic infiltration of MCs. CM typically presents as UP and is a benign disease confined to the skin. In many cases, particularly in children, this disease regresses spontaneously. By contrast, SM is a clonal persistent disease of MC-committed or precommitted hematopoietic progenitors. In most of these patients, the transforming c-kit mutation Asp-816-Val is detectable. The clinical course in SM is variable. Many cases remain in an indolent stage over decades. In a few patients, significant organopathy is found, and this may lead to the diagnosis of aggressive SM. In other patients, AHNMD is diagnosed. MCL is a rare form of SM characterized by leukemic spread of MCs in the marrow and blood and rapid progression. In contrast to indolent SM, patients with MCL or aggressive SM often present without UP-like skin lesions. Patients with indolent SM should be treated with mediator-targeting drugs but not with cytoreductive drugs. By contrast, patients with aggressive SM or MCL are candidates for cytoreductive therapy. Some patients with aggressive SM may benefit from IFNalpha2b. Patients with rapid progression or MCL are candidates for more aggressive treatment, including cladribine, chemotherapy, and stem cell transplantation. In patients with SM-AHNMD, the SM should be treated as if no AHNMD is present, and the AHNMD should be treated as if no SM had been diagnosed.
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PMID:Mast cell proliferative disorders: current view on variants recognized by the World Health Organization. 1456 Jul 84

In mast cell (MC) disorders (mastocytosis), clinical symptoms are caused by the release of chemical mediators from MCs, the pathologic infiltration of neoplastic MCs in tissues, or both. Cutaneous mastocytosis is a benign disease in which MC infiltration is confined to the skin. In pediatric cases cutaneous mastocytosis might regress spontaneously. Systemic mastocytosis (SM) is more frequently diagnosed in adults and is a persistent (clonal) disease of bone marrow-derived myelomastocytic progenitors. The somatic c-kit mutation D816V is found in the majority of such patients. The natural clinical course in SM is variable. Whereas most patients remain at the indolent stage for many years, some have aggressive SM (ASM) at diagnosis. Other patients have an associated clonal hematologic non-MC lineage disease (AHNMD). MC leukemia (MCL) is a rare disease variant characterized by circulating MCs and fatal disease progression. The diagnoses of ASM, SM-AHNMD, and MCL might be confused with a variety of endocrinologic, vascular, or immunologic disorders. It is therefore of particular importance to be aware of the possibility of an underlying (malignant) MC disease in patients with unexplained vascular instability, unexplained (anaphylactoid) shock, idiopathic flushing, diarrhea, headache, and other symptoms that might be mediator related. An important diagnostic clue in such cases is an increased serum tryptase level. The current review provides an overview of mastocytosis and its subvariants and a practical guide that might help to delineate mastocytosis from unrelated systemic disorders.
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PMID:Diagnosis and classification of mast cell proliferative disorders: delineation from immunologic diseases and non-mast cell hematopoietic neoplasms. 1524 37

Mast cell disorders are defined by an abnormal accumulation of tissue mast cells (MCs) in one or more organ systems. Symptoms in mastocytosis result from MC-derived mediators and, less frequently, from destructive infiltration of MCs. Cutaneous mastocytosis (CM) is a benign disease of the skin and may regress spontaneously. Systemic mastocytosis (SM) is a persistent disease in which a somatic c-kit mutation at codon 816 is usually detectable in MCs and their progenitors. The clinical course in these patients is variable ranging from asymptomatic for years to highly aggressive and rapidly devastating. The WHO discriminates five categories of SM: indolent SM (ISM), aggressive SM (ASM), SM with associated clonal hematological non-MC-lineage disease (AHNMD), and mast cell leukemia (MCL). The c-kit mutation D816V is quite common and may be found in all SM-categories. In SM-AHNMD, additional genetic abnormalities have been reported, whereas no additional defects are yet known for ASM or MCL. Patients with ISM and CM are treated with "mediator-targeting" drugs, whereas patients with ASM or MCL are candidates for cytoreductive therapy. The use of "Kit-targeting" tyrosine kinase inhibitors such as STI571 (Imatinib, Gleevec), has also been suggested. However, the D816V mutation of c-kit is associated with relative resistance against STI571. Therefore, these patients require alternative targeted drugs or new drug-combinations. In patients with SM-AHNMD, separate treatment plans for the SM-component and the AHNMD should be established. Examples include the use of STI571 in patients with SM plus hypereosinophilic syndrome (SM-HES) and the FIPL1/PDGFRA fusion gene target, or chemotherapy for eradication of AML in patients with SM-AML.
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PMID:Mastocytosis: pathology, genetics, and current options for therapy. 1562 79

Systemic mast cell disorders in most instances appear to be clonal disorders of the mast cell and its progenitor. Symptoms result from a pathological release of mast cell mediators and a destructive mast cell infiltration. Cutaneous mastocytosis is most frequently seen in children and may regress. Systemic mastocytosis (SM) is a persistent disease. A somatic c-kit mutation at codon 816 is often detectable in haematopoietic cells. The clinical course of mastocytosis is variable, ranging from indolent to aggressive. Five categories of disease are recognized: Indolent SM, aggressive SM, SM with associated clonal haematological non-mast cell-lineage disease (AHNMD) and mast cell leukaemia (MCL). In SM-AHNMD, additional genetic abnormalities have been reported. Patients with cutaneous or indolent systemic disease are treated symptomatically. Patients with aggressive disease are candidates for cytoreductive therapy. The use of 'Kit-targeting' tyrosine kinase inhibitors are best selected following a mutational analysis of c-kit. For instance, the D816V mutation appears to be associated with relative resistance against imatinib. However, imatinib has been used with success in patients with SM-hypereosinophilic syndrome (HES) and the FIPL1/PDGFRA fusion gene and in a patient with mastocytosis with a mutation outside of codon 816. The value of bone marrow transplantation remains under investigation.
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PMID:Mastocytosis. 1660 39

Mastocytosis is a neoplastic disease involving mast cells (MC) and their CD34+ progenitors. Symptoms in mastocytosis are caused by biological mediators released from MC and/or the infiltration of neoplastic MC in various organs, the skin and the bone marrow being predominantly involved. A WHO consensus classification for mastocytosis exists, which is widely accepted and includes three major categories: (1) Cutaneous mastocytosis (CM), a benign disease in which MC infiltration is confined to the skin, is preferentially seen in young children and exhibits a marked tendency to regress spontaneously. (2) Systemic mastocytosis (SM) which is commonly diagnosed in adults and includes four major subtypes: (i) indolent SM (ISM, the most common form involving mainly skin and bone marrow); (ii) a unique subcategory termed SM with an associated non-mast cell clonal hematological disease (SM-AHNMD); (iii) aggressive SM usually presenting without skin lesions, and (iv) MC leukemia, probably representing the rarest variant of human leukemias. (3) The extremely rare localized extracutaneous MC neoplasms, either presenting as malignancy (MC sarcoma) or as benign tumor termed extracutaneous mastocytoma. Diagnostic criteria for mastocytosis are available and are widely accepted. SM criteria include one major criterion (multifocal compact tissue infiltration by MC) and four minor criteria: (1) prominent spindling of MC; (2) atypical immunophenotype of MC with coexpression of CD2 and/or CD25 (antigens which have not been found to be expressed on normal/reactive MC); (3) activating (somatic) point mutations of the c-kit proto-oncogene usually involving exon 17, with the imatinib-resistant type D816V being most frequent, and (4) persistently elevated serum tryptase level (>20 ng/ml). To establish the diagnosis of SM, at least one major and one minor criterion, or at least three minor criteria, have to be fulfilled. The natural clinical course of mastocytosis is variable. Most patients, in particular those with CM and ISM, remain in an indolent stage over many years or even decades, while others, in particular those with aggressive SM, SM-AHNMD, or mast cell leukemia, show a progressive course, usually with a fatal outcome.
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PMID:Mastocytosis: state of the art. 1758 83

An elderly woman presented with anaemia, thrombocytopenia and multifocal lytic and sclerotic bone lesions. Trephine bone marrow biopsy demonstrated widespread involvement by systemic mastocytosis (SM). The neoplastic mast cells expressed mast cell tryptase, CD117, CD25 and CD9, and were accompanied by compact sheets of atypical large histiocytic cells, expressing CD68, CD4, S-100 protein and CD14, in keeping with a concomitant histiocytosis (SM-AHNMD). Mutation analysis revealed the activating point mutation D816V of the c-kit proto-oncogene in microdissected pooled bone marrow mast cells. Partial remission was achieved using interferon alpha. To the best of our knowledge this is the first reported case of SM-AHNMD with histiocytosis as the non-mast cell component.
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PMID:Systemic mastocytosis (SM) and associated malignant bone marrow histiocytosis - a hitherto undescribed form of SM-AHNMD. 2186 66