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)

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

Mastocytosis are characterized by an accumulation of abnormal mast cells in various tissues. Their incidence is estimated at 1/150,000 patients. Pure cutaneous mastocytosis which are mainly observed during childhood may resolve spontaneously during adolescence, whereas systemic mastocytosis involving one or more organs or tissues are more observed in adults. The initial event leading to mastocytosis is believed to be related to activating mutations in c-kit receptor, thus resulting in increased proliferation of mast cells precursors, migration in various tissues and degranulation leading to clinical signs. This nosologic entity does not belong to allergic diseases. Their perioperative management involves a multidisciplinary approach. The degranulation of mast cells with subsequent clinical symptoms can be triggered by psychological, chemical, traumatic, physical (rubbing, extreme temperatures...) agents. Avoiding these triggers should be realized whenever possible according to each patient. The premedication has not proven its efficiency. Tryptase measurement is part of the preoperative biological assessment. The clinical signs severity is related to the cardiovascular homeostasis disturbances (arterial hypotension, cardiovascular collapse, cardiac arrest). The cardiovascular symptoms do not correlate to the cutaneous versus systemic description of the disease. The drug of choice for the treatment of the severe cardiovascular signs is epinephrine associated to vascular loading. The aim of this literature review is to suggest the different modalities of perioperative care of patients with mastocytosis.
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PMID:[Mastocytosis and anaesthesia]. 1909 49

Mastocytosis is a heterogeneous entity that may present as either a cutaneous or systemic disease. Progression of pediatric cutaneous mastocytosis (CM) is uncommon, but in adults, this condition persists and often progresses to systemic disease. Mast cell proliferation and differentiation from stem cell precursors depend on a number of factors, including a mast cell tyrosine kinase receptor (kit) and its ligand (the stromal cell-derived cytokine stem cell factor). A gain-of-function mutation in codon 816 of c-kit is frequently present in mast cells of patients with systemic mastocytosis (SM). The diagnostic approach for a patient with suspected mast cell disease includes a thorough skin examination, a skin biopsy, a serum tryptase level, and bone marrow aspiration and biopsy. The treatment is directed toward avoidance of triggers of mast cell mediator release and management of symptoms. Aggressive cases are managed with cytoreductive therapies, such as interferon alfa-2b and cladribine. Research has been directed at more specific treatment modalities, including specific kit tyrosine kinase inhibitors.
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PMID:Systemic mastocytosis: classification, pathogenesis, diagnosis, and treatment. 1927 68

Mastocytosis is a proliferative disorder of the hematopoietic mast cell progenitor that results from expansion of a clone carrying the D816V c-kit mutation. Based on the dramatic increase in incidence of anaphylaxis in patients with mastocytosis, recent studies analyzed the presence of clonal mast cell markers, including D816V c-kit mutation, in patients with recurrent IgE- and non-IgE-mediated anaphylaxis. These studies demonstrated the presence of an aberrant mast cell clone in a significant proportion of patients with unexplained anaphylaxis, or anaphylaxis due to hymenoptera venom. Clonal mast cell disease should be suspected in particular in patients presenting with profound cardiovascular manifestations such as hypotension and syncope in the absence of urticaria.
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PMID:Anaphylaxis and mast cell disease: what is the risk? 2042 12

Mastocytosis is a disorder characterized by increased numbers of mast cells in tissues. Recent clinical observations highlight the association of mastocytosis with an increased risk of anaphylaxis and underline the diversity of this disease. At the molecular level, recent studies have attempted to unravel specific gene expression profiles for activating c-kit mutations in the etiology of mastocytosis. The diagnosis may be facilitated by surrogate markers and detection of aberrant immunophenotypic surface markers. New therapeutic strategies are in development based on intracellular signal pathways, or on application of topical treatments, as are novel forms of cytoreductive therapy, including tyrosine kinase inhibitors.
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PMID:Update on diagnosis and treatment of mastocytosis. 2152 72

Mastocytosis is a heterogeneous disease characterized by the accumulation of mast cells in one or more organs. Our objective was to identify a peripheral mast cell precursor and assess its variation rate in mastocytosis. A peripheral blood phenotypic analysis was performed among 50 patients with mastocytosis who were enrolled in a prospective multicentric French study, and the phenotypic analysis results of the patients were compared with those of healthy donors. The rate of peripheral blood CD34(-)c-Kit(+) cells correlated with the severity of mastocytosis. This cellular population was isolated from healthy donors as well as from patients with systemic mastocytosis. After 30 days of culture, the CD34(-)c-Kit(+) cells gave birth to mature mast cells, indicating that this cellular population constitutes a mast cell circulating precursor. Monitoring peripheral CD34(-)c-Kit(+) cells by flow cytometry could be a useful and low-invasive tool to determine the disease severity and the relapses and to assess treatment efficiency.
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PMID:Blood CD34-c-Kit+ cell rate correlates with aggressive forms of systemic mastocytosis and behaves like a mast cell precursor. 2187 76

Mastocytosis is a group of disorders characterized by abnormal mast cell proliferation, involving the skin in 80% of cases. Cutaneous mastocytosis, which appears in childhood in 60% of cases, usually has a benign course with a gradually regressive evolution before puberty. Mast cell sarcomas, part of the systemic forms of mastocytosis, are very rare tumors characterized by a destructive growth of highly atypical mast cells, with secondary spread, poor prognosis, and low survival rates. We report the first known case of primary cutaneous mast cell sarcoma due to the transformation of a benign solitary mastocytoma in an adult suffering from an unregressive localized cutaneous mastocytosis. Histologic characteristics of the tumor, mutation analysis, and c-Kit expression were compared with available data. Wide surgical excision of the tumor followed by adjuvant local radiotherapy were performed, and for the first time the use of imatinib was attempted, as neoplastic mast cells expressed the CD117 marker. However, they failed to control the progression of sarcoma. To date, no treatment is known to be effective for this disease, which is associated with short-term survival of the patients.
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PMID:Malignant transformation of mastocytoma developed on skin mastocytosis into cutaneous mast cell sarcoma. 2249 28

Mastocytosis is a heterogenous disorder due to abnormal proliferation and infiltration of mast cells in different tissues, primarily the skin and the bone marrow. Cutaneous mastocytosis is often benign and regresses spontaneously. Systemic mastocytosis is a chronic disease in which some types are indolent but other types such as mast cell leukemia are very aggressive. Pathogenesis of systemic mastocytosis involves a somatic mutation of the gene coding for the c-kit receptor, the most frequent mutation being D816V. Diagnostic criteria have been established by the WHO using histopathological, molecular and biochemical parameters. Treatment of systemic mastocytosis remains a challenge for the clinician due to variability and complexity of the disease. There is, in addition, a lack of a standard and efficient treatment. New targeted therapies with tyrosine kinase inhibitors directed against the c-kit receptor are currently being studied, with the purpose to act specifically on the " primum movens "of the disease. The current review provides an overview of pathogenesis, clinical presentation, diagnosis and classification of cutaneous and systemic mastocytosis. We also discuss the prognosis and the different treatments currently available according to the sub-type of mastocytosis.
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PMID:[Mastocytosis: revisited with new cytogenetic data]. 2251 45

Mastocytosis is a rare condition related to an abnormal proliferation of mast cells and their accumulation in tissues. Cutaneous mastocytosis is the most common form and mainly affects newborns and infants. The symptoms are caused by the release of mediators contained in mast cells, including histamine. Mastocytosis may be associated with a mutation in the gene encoding the c-kit receptor. Clinically, there are different dermatological findings, which combine acute cutaneous, digestive, or even hemodynamic manifestations in varying degrees. The diagnosis is confirmed by the histological study of a skin sample. We report here the case of a 4-month-old infant suffering from diffuse cutaneous bullous mastocytosis, a very rare variety of mastocytosis. This infant had an erosive and bullous manifestation of dermatosis, initially confused with impetigo. The proliferation of bullous lesions led to her hospitalization. Codeine intake for pain was responsible for a large and extensive bullous reaction associated with anaphylactic shock. This context of bullous spread occurring after taking codeine led to the suspicion of bullous diffuse cutaneous mastocytosis, a diagnosis that was confirmed histologically. This observation demonstrates the difficulty of mastocytosis diagnosis, mostly due to its rarity, especially in its diffuse bullous forms. The rapid deterioration of this patient, after the codeine prescription, emphasizes the importance of the eviction of histamine-releaser compounds in the management of this disease.
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PMID:[Bullous mastocytosis in infancy: a rare presentation]. 2266 34

Cutaneous mastocytosis is a rare clinically heterogeneous disorder characterized by mast cell infiltration. Mastocytosis affects both children and adults and has been reported to occur in families. Recent data suggest that mutations in the c-kit proto-oncogene are causative of mastocytosis not only in adults but in children and familial cases as well; however, mutation analysis other than D816V is not widely available, making detection of causative mutations problematic. We present the case of a 33-year-old man with a 30-year history of persistent urticaria pigmentosa and his 2 affected children. Sequencing of KIT exons 8, 10, 11, and 17 was carried out on a skin biopsy specimen and mucosal swabs of the incident case and was negative for known KIT mutations. Additional work-up was deferred by the family. Presentation of this familial case of urticaria pigmentosa demonstrates the complexity of genetic evaluation in clinical settings. It suggests that mutations other than those reported in exons 8, 10, 11, and 17 may also result in familial mastocytosis. Presentation of this case also allows for review of the mechanism of action of causative KIT mutations and the recent literature supporting KIT mutations in childhood and familial mastocytosis.
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PMID:Familial urticaria pigmentosa: report of a family and review of the role of KIT mutations. 2289 71


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