Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mastocytosis are a group of diseases characterized by abnormal proliferation of mast cells. Various forms are observed in respect to the organ system involving, clinical manifestations, and association with hematological disorders. The c-kit proto-oncogene encodes for a receptor tyrosine kinase, which plays a crucial role in hematopoiesis, especially in mast cell growth and differentiation. Mutations in the tyrosine kinase domain of c-kit have been reported in murine and human malignant cell lines, and more recently in some cases of human mast cell diseases. The biochemical and clinical aspects of these mutations are reviewed with special emphasis on the experiments which demonstrate their role in oncogenesis and mast cell proliferation.
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PMID:C-kit mutations and mast cell disorders. A model of activating mutations of growth factor receptors. 916 10

A 5-month-old Hispanic boy had a diffuse eruption and massive peripheral eosinophilia. Mastocytosis was diagnosed by skin biopsy and Giemsa stain. Other causes of eosinophilia were ruled out by bone marrow examination and negative cultures. The patient's course improved with antihistamines and the removal of mast cell degranulating agents. Clinicians need to be aware that mastocytosis should be considered in the differential diagnosis of eosinophilia.
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PMID:Urticaria pigmentosa presenting with massive peripheral eosinophilia. 926 9

Mastocytosis is a term used for a spectrum of disorders characterized by abnormal growth and accumulation of mast cells. The cutaneous variants of the disease have to be distinguished from systemic mastocytosis (SM), in which at least one extracutaneous organ is involved. In contrast to cutaneous mastocytosis, SM is often associated with another hematologic neoplasm. In most cases clonal myeloid malignancies such as a myeloproliferative or myelodysplastic syndrome occur. In a few cases of SM, however, clonal lymphoid disorders have been described. We here report on a case of SM associated with multiple myeloma. At first presentation, the 48-year old female patient showed monoclonal IgGlambda gammopathy and bone marrow (BM) mastocytosis, but no BM plasma cell infiltrates. Eight years later, the patient presented with BM mastocytosis and overt multiple myeloma. The co-existence of myeloma and mastocytosis was demonstrable by staining serial BM sections with antibodies against mast cell tryptase, CD68R, and the plasma cell marker VS38c. Interphase FISH analysis of BM sections revealed a numeric gain of chromosome 5 and chromosome 7 in the plasma cells but not in the mast cell infiltrates, thereby confirming the presence of two different neoplastic cell populations. To our knowledge, this is the first report describing the co-existence of multiple myeloma and mastocytosis.
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PMID:A case of bone marrow mastocytosis associated with multiple myeloma. 961 35

Mastocytosis is a rare disorder with serious anaesthetic implications. Anaesthetic management is hazardous since trauma, stress, extremes of temperature and drugs may precipitate intra-operative mast cell degranulation. Release of histamine and other mast cell mediators can lead to profound cardiovascular collapse and even death. We present a case report of a patient with mastocytosis who suffered cardiac arrest during anaesthesia. Anaphylactoid/anaphylactic shock may be delayed and lack supporting signs of histamine release such as cutaneous flushing and bronchospasm.
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PMID:Systemic mastocytosis presenting as profound cardiovascular collapse during anaesthesia. 979 25

Mastocytosis represents a mast cell proliferative disease that generally runs a benign clinical course, with spontaneous remissions mostly by puberty in childhood-onset disease, although rare forms, particularly in adult-onset disease, can be associated with (pre)malignant hematologic disorders and very rarely present as mast cell leukemia or malignant mastocytosis. Reasons for this divergent clinical behavior of childhood- versus adult-onset disease are unknown. Recently, two activating mutations in the intracellular domain of the proto-oncogene c-kit, which encodes a tyrosine kinase receptor for the mast cell growth factor stem cell factor, have been detected in the human leukemic mast cell line HMC-1. We have therefore studied lesional skin biopsies from patients with adult- and childhood-onset indolent mastocytosis for the presence of these codon 560 and 816 mutations. C-kit coding DNA sequences were amplified and analyzed by mutation-specific restriction analyses, and mutated polymerase chain reaction products were additionally cloned and sequenced. The codon 816 mutation was found in all six samples from adult patients, but not in any of the 11 specimens from children. In addition, the codon 560 mutation could be demonstrated for the first time in indolent mastocytosis, namely in two of four specimens from adult patients, but not in those from two children. These data thus provide a possible explanation for the divergent clinical behavior of adult- versus childhood-onset indolent mastocytosis, with the first being associated with an activating mutation, possibly as part of a neoplastic process, and the latter representing most likely a reactive process of an as yet unknown pathogenesis.
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PMID:Identification of activating c-kit mutations in adult-, but not in childhood-onset indolent mastocytosis: a possible explanation for divergent clinical behavior. 985 47

Mastocytosis is characterized by an excessive number of apparently normal mast cells in the skin and, occasionally, in other organs. Characteristic skin lesions, called urticaria pigmentosa, are present in most patients, but clinical presentation can vary from a pruritic rash to unexplained collapse and sudden death. These lesions are typically tan to red-brown macules that appear on the trunk and spread symmetrically. Patients with mastocytosis often have a long history of chronic and acute symptoms that were unrecognized as mastocytosis. Skin lesions may or may not accompany systemic mastocytosis. Systemic disease may involve the gastrointestinal tract, the bone marrow or other organs. Even when the disease is considered as a possibility by the physician, the diagnosis can be difficult because of special technical requirements necessary for biopsy and because of the problems with biochemical testing. Drug therapy is initiated to stabilize mast cell membranes, to reduce the severity of the attacks and to block the action of inflammatory mediators. The mainstay of therapy is histamine H1 and H2 blockers and the avoidance of triggering factors.
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PMID:Cutaneous and systemic manifestations of mastocytosis. 1039 89

Mastocytosis is a neoplastic disease caused at least in part by somatic mutations of the c-KIT proto-oncogene resulting in constitutive activation of its protein product, KIT, the receptor tyrosine kinase for stem cell factor. KIT stimulates mast cell proliferation and prevents apoptosis of neoplastic mast cells. To develop potential therapies for mastocytosis we used indolinones, small molecules that inhibit tyrosine kinases. Four indolinone derivatives (SU4984, SU6663, SU6577, and SU5614) inhibited wild-type KIT, but variably inhibited constitutively activated KIT mutants. SU4984, SU6577, and SU5614 were effective against KIT with juxtamembrane activating mutations, whereas only SU6577 could suppress KIT containing either juxtamembrane or kinase domain activating mutations. Furthermore, SU4984, SU6577, and SU5614 killed neoplastic mast cells expressing a juxtamembrane-mutated KIT, whereas SU4984 and SU6577 killed neoplastic mast cells expressing KIT bearing a kinase domain mutation. These data show a direct correlation between inhibition of constitutively activated KIT and the death of neoplastic mast cells, and point to specific tyrosine kinase inhibitors as a potential therapy aimed directly at a cause of mastocytosis.
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PMID:Indolinone derivatives inhibit constitutively activated KIT mutants and kill neoplastic mast cells. 1065 4

Mastocytosis encompasses a range of disorders characterized by overproliferation and accumulation of tissue mast cells. Mast cell disease is most commonly seen in the skin, but the skeleton, gastrointestinal tract, bone marrow, and central nervous system may also be involved. We present a 10-year-old boy with diffuse cutaneous mastocytosis characterized by disseminated papular, nodular, and infiltrated leathery lesions. The patient presented with chronic diarrhea and malnutrition. Laboratory studies were normal except for an elevated urinary 1-methylhistamine level. The bone marrow aspirate showed a dense mast cell infiltrate confirming systemic involvement.
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PMID:Diffuse cutaneous mastocytosis with bone marrow infiltration in a child: a case report. 1088 51

Mastocytosis is a disease characterized by excessive accumulation of mast cells in different tissues and symptoms caused by the release of mast cell mediators. The skin is frequently directly involved in mastocytosis. The disease is rarely seen in other members of the subjects' family; only 49 cases of familial mastocytosis have been reported. Familial mastocytosis associated with hearing loss may represent a newly described inherited entity. We describe a brother and sister exhibiting skin mastocytosis and neurosensory deafness, associated with a history of hearing loss in their father's family. The appearance of the mast cell disease in two siblings, who presented with similar clinical features represents a familial form of mastocytosis; the association with an inherited form of deafness may constitute a new syndrome. Our patients show several features similar to some previously reported cases but different insofar that additional congenital defects and mental retardation are absent.
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PMID:Familial mastocytosis associated with neurosensory deafness. 1097 97

Mastocytosis is a rare disease characterized by a primary pathological increase in mast cells in different tissues, which may present in a variety of clinical patterns. Major advances have been made in recent years in the understanding of the pathogenesis of mastocytosis. This review is aimed at familiarizing dermatologists with these recent findings, and at exploring their possible implications for the diagnosis and treatment of the condition. The heterogeneous clinical presentation of mastocytosis is detailed with respect to the type of skin lesions, age at onset, family history, organ systems involved, associated haematological disorders and prognosis. Recent genetic findings also indicate different pathogenetic forms of mastocytosis, as adult patients and those with associated haematological diseases usually express activating mutations of the stem cell factor receptor c-kit, whereas most cases of childhood-onset and familial mastocytosis seem to lack these mutations. Despite the presence of c-kit mutations, patients with cutaneous lesions generally have a good prognosis, even when there is involvement of other organs. Some patients, particularly those with childhood-onset disease, experience spontaneous remission, mostly by puberty. c-kit mutations do not explain the initial cause of mastocytosis, and their prognostic significance is as yet unclarified, as is the pathogenesis in patients without the mutations. Furthermore, these novel findings have as yet not resulted in a more effective treatment of the cause of the disease, so that counselling, prevention of exposure to mast cell secretory stimuli, and symptomatic treatment remain the mainstays of current patient management.
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PMID:Mastocytosis: recent advances in defining the disease. 1129 25


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