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 comprises several diseases characterized by an abnormal increase in tissue mast cells. Cutaneous mastocytosis (CM) is the most common form of mastocytosis, affects predominantly children, and presents as a mast cell hyperplasia limited to the skin. Systemic mastocytosis (SM) comprises multiple distinct entities in which mast cells in filtrate the skin and/or other organs. The diagnosis of SM is based on the presence of one major criterion and one minor criterion or three minor criteria. Major criteria include the presence of multifocal dense infiltrates of > 15 mast cells in bone marrow and/or other extracutaneous organs. Four minor criteria include the presence of elevated serum alpha-tryptase levels > 20 ng/mL, the expression of CD2 and CD25 surface markers in c-kit-positive mast cells from bone marrow or other organs, the presence of a c-kit mutations on bone marrow and/or other tissues mast cells, and the presence of > 25% abnormal spindle-shaped mast cells in bone marrow and/or tissues. Symptoms of CM include pruritus, flushing urticaria, and dermatographism. Symptoms of SM include cutaneous symptoms in association with syncope, gastric distress, nausea and vomiting, diarrhea, bone pain, and neuropsychiatric symptoms. Activating and nonactivating mutations of c-kit (Asp816Val) are seen in adult SM and in some pediatric CM (Gly839Lys), indicating a clonal dysregulation. There is no cure for mastocytosis but the majority of pediatric CM regress at puberty. Women with mastocytosis are fertile and pregnancy and delivery have been successful by blocking mast cell-mediated symptoms. Symptomatic treatment aimed at reducing the effect of mediators is effective with antihistamines and mast cell-stabilizing agents such as sodium cromolyn. To reduce mast cell burden, interferon alpha, steroids, and purine analogs have been used with varying results. Future directions include tyrosine kinase inhibitors and bone marrow transplant.
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PMID:Mastocytosis: classification, diagnosis, and clinical presentation. 1505 60

Mutational analysis of the c-kit gene in a patient with a previously undescribed variant of mast cell disease revealed a germline mutation, Phe522Cys, within the transmembrane portion of the Kit receptor protein. Transfection experiments revealed that the mutation caused ligand-independent autophosphorylation of Kit, which was inhibited by the tyrosine kinase inhibitor imatinib mesylate. The patient's bone marrow biopsy and aspirate displayed unique pathologic features with the presence of excessive numbers of mature-appearing mast cells and absence of aberrant mast cell surface expression of CD2, CD25, and CD35. Therapy with imatinib mesylate resulted in a dramatic improvement in mast cell burden and clinical symptoms. These results highlight the significance of the transmembrane region of Kit in activation of the molecule and its importance in mast cell development and suggest a role for screening for transmembrane c-kit mutations in patients with mastocytosis in association with the decision to use imatinib mesylate.
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PMID:A novel form of mastocytosis associated with a transmembrane c-kit mutation and response to imatinib. 1507 Jul 6

In the vast majority of patients with systemic mastocytosis (SM), the bone marrow is the primary extracutaneous site of disease. In addition to bone marrow involvement, other visceral organs such as the spleen, liver or the gastrointestinal tract, may also be affected. However, isolated involvement of a single extramedullary organ is rarely seen in SM. We report on two patients with SM with splenic involvement, lack of 'diagnostic' mast cell (MC) infiltrates in the bone marrow, and absence of skin lesions. In one patient, a myelodysplastic syndrome was diagnosed prior to the detection of SM. Both patients presented with massive splenomegaly and multifocal MC infiltrates in splenic tissues. These MCs also expressed CD25 as well as the C-KIT mutation D816V. In consecutive examinations, the mutation was also detected in the bone marrow in both patients suggesting diffuse infiltration with neoplastic cells. In summary, our data show that the spleen can be a primary site of disease in rare cases of SM. Mastocytosis should therefore be considered as a (rare) differential diagnosis in patients with splenomegaly of unknown etiology.
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PMID:Splenic mastocytosis: report of two cases and detection of the transforming somatic C-KIT mutation D816V. 1516 Sep 46

An association between mastocytosis and monoclonal gammopathy is a relatively rare but well recognized clinical finding. In the majority of cases, however, overt myeloma or lymphoma is not detectable morphologically. Here we describe the case of a 51 year-old male patient first presenting with paresis of the right facial nerve and the serological finding of IgM kappa paraproteinemia. The patient did not have organomegaly, lytic bone lesions, or urticaria pigmentosa-type skin lesions. Histological examination of a trephine biopsy specimen revealed the unusual coexistence of plasma cell myeloma and mastocytosis. Immunohistochemically, plasma cells were found to exhibit a monotypic staining for Ig heavy chain mu and Ig light chain kappa, thus confirming their neoplastic nature. Mast cells showed prominent spindling and formed dense multifocal infiltrates, thus enabling the diagnosis of bone marrow mastocytosis. Immunohistochemically, mast cells expressed tryptase, chymase, and KIT (CD117). In addition, aberrant expression of CD25 on mast cells was detected, confirming the coexistence of a neoplastic mast cell-proliferative disorder. According to the WHO proposal for classification of hematopoietic malignancies, this unique case, showing the association of two very rare haematologic neoplasms, can therefore best be referred to as bone marrow mastocytosis associated with IgM kappa plasma cell myeloma (SM-AHNMD).
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PMID:Bone marrow mastocytosis associated with IgM kappa plasma cell myeloma. 1516 Sep 59

The aberrant co-expression of CD2 and CD25 antigens is the immunophenotypic hallmark of neoplastic mast cells, and has been consistently identified on bone marrow mast cells from patients with indolent mast cell disease (MCD). We prospectively analyzed the bone marrow mast cell immunophenotype by multiparametric flow cytometry (FC) for 33 MCD cases, to examine the role of CD2 and CD25 expression in establishing diagnosis, detecting histologically occult bone marrow mast cell infiltration, and assessing treatment response. While CD25 was almost uniformly expressed, only 6 of 13 patients with indolent MCD, 1 of 8 with aggressive MCD, 2 of 7 with MCD and an associated hematological disorder, and none of the 2 patients with either mast cell leukemia or smoldering systemic mastocytosis, expressed CD2. One of three patients with cutaneous mastocytosis had an aberrant CD2+/CD25+ mast cell population suggesting histologically occult bone marrow involvement. CD25 expression was lost in one patient who achieved complete histologic remission with therapy, but not in two patients who achieved a partial remission. In conclusion, CD25, but not CD2, is a reliable marker for neoplastic mast cells, and CD25 expression indicates histologically occult bone marrow infiltration and residual disease after therapy.
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PMID:Bone marrow mast cell immunophenotyping in adults with mast cell disease: a prospective study of 33 patients. 1520 75

Specific allergen injection immunotherapy is highly effective in IgE-mediated diseases, such as allergic rhinitis and venom anaphylaxis. Immunotherapy inhibits both early and late responses to allergen exposure. Immunotherapy is accompanied by increases in allergen-specific IgG, particularly the IgG4 isotype, which blocks not only IgE-dependent histamine release from basophils but also IgE-mediated antigen presentation to T cells. Immunotherapy acts on T cells to modify peripheral and mucosal T(H)2 responses to allergen in favor of T(H)1 responses. Recent studies have identified increased IL-10 production in peripheral blood and mucosal surfaces after immunotherapy. IL-10 has numerous potential antiallergic properties, including suppression of mast cell, eosinophil, and T-cell responses, as well as acting on B cells to favor heavy chain class switching to IgG4. These IL-10-producing cells might be so-called regulatory T cells and appear to be identified by the CD4(+)CD25(+) phenotype. Studies in mice suggest that dendritic cells play a vital role in induction of regulatory T cells. Novel approaches to immunotherapy currently being explored include the use of adjuvants, such as monophosphoryl lipid A or nucleotide immunostimulatory sequences derived from bacteria that potentiate T(H)1 responses. Alternative strategies include the use of allergen-derived peptides or modified recombinant allergen vaccines that act on T cells while minimizing the IgE-dependent mast cell activation that is dependent on the native allergen conformation.
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PMID:Mechanisms of immunotherapy. 1520 78

The diagnosis of systemic mastocytosis (SM) is based primarily on the histologic and immunohistochemical evaluation of a bone marrow trephine biopsy specimen. Although mast cell (MC) specific antigens like tryptase and chymase are detectable in routinely processed tissue, no immunohistochemical markers that can be used to discriminate between normal and neoplastic MCs are yet available. We have investigated the diagnostic value of an antibody against CD25 for the immunohistochemical detection of MCs in bone marrow sections in 73 patients with SM and 75 control cases (reactive marrow, n = 54; myelogenous neoplasms, n = 21) and correlated the results with the presence of c-kit mutations. While MCs in almost all patients with SM (72 of 73) expressed CD25, none of the control samples contained CD25-positive MCs. Irrespective of the SM subtype, most of neoplastic MCs expressed CD25. In 3 patients with advanced MC disease, pure populations of neoplastic MCs were obtained and found to express CD25 mRNA by RT-PCR analysis. In addition, all patients with CD25-positive MCs contained c-kit mutations, while all control cases exhibited wild type c-kit. CD25 therefore appears to be a reliable immunohistochemical marker for the discrimination of neoplastic from normal/reactive MCs, with potential as a diagnostic tool in SM.
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PMID:CD25 indicates the neoplastic phenotype of mast cells: a novel immunohistochemical marker for the diagnosis of systemic mastocytosis (SM) in routinely processed bone marrow biopsy specimens. 1537 47

Mastocytosis comprises a heterogeneous group of disorders characterized by proliferation and accumulation of mast cells in 1 or more organ systems. Mast cell leukemia (MCL) is an extremely rare subtype of mastocytosis in which a leukemic spread of mast cells and a rapid progression of disease is seen. In typical cases, mast cells are found in the peripheral blood. However, an aleukemic variant of MCL (formerly termed malignant mastocytosis) has also been described. We here report a case of aleukemic MCL with abnormal immunophenotype of mast cells and the classical c-kit point mutation Asp-816-Val (=D816V). The 75-year-old male patient had a short history of weight loss and lymphadenopathy. There were no urticaria pigmentosa-like skin lesions. The bone marrow was diffusely infiltrated with atypical mast cells that comprised more than 80% of all nucleated cells on a bone marrow smears. As assessed by immunohistochemistry, neoplastic mast cells expressed tryptase, chymase, CD2, CD25, CD68, and the KIT protein (CD117). Mutation analysis revealed the c-kit mutation D816V. Since circulating mast cells could not be detected in the peripheral blood, the diagnosis of aleukemic MCL was established in accordance to the updated WHO consensus classification. This case further supports the notion that the pathogenesis (c-kit mutation D816V) in MCL is closely related to that found in indolent mast cell disorders. However, additional (but yet unknown) molecular (genetic) defects have to be considered to explain the extremely heterogenous clinical course in these patients.
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PMID:Aleukemic mast cell leukemia with abnormal immunophenotype and c-kit mutation D816V. 1551 20

The clinical spectrum of mast cell disease ranges from relatively innocuous and histologically subtle urticarial skin lesions to an aggressive and fatal leukemic form of mast cell proliferation. Not surprisingly, mast cell infiltrates may show significant microscopic heterogeneity, particularly in the bone marrow, the most common site of involvement in systemic mastocytosis (SM). Herein, 3 cases are presented to illustrate the clinical and morphologic heterogeneity of mast cell disease: the first patient, with long standing urticaria pigmentosa, developed anemia and thrombocytopenia; the second patient presented with a pathologic fracture; and the third patient was suspected to have refractory anemia. Upon bone marrow examination, all 3 patients showed mast cell infiltration with distinct morphologic features and all met the WHO criteria for aggressive systemic mastocytosis. Histochemical methods continue to play a role in the identification of mast cells, with some limitations depending on the degree of differentiation of the mast cells and tissue processing methods. Immunohistochemistry has contributed to the identification of mast cells. Coexpression of CD117 and CD25, as well as expression of the more specific immunohistochemical marker tryptase, is seen in systemic SM. The latter may also be employed as a serum marker in the diagnosis and follow-up of patients with SM. The mast cells, in the majority adults with SM, have somatic point mutations of KIT.
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PMID:The faces of mast cell disease: bone marrow infiltrates in 3 patients with systemic mastocytosis. 1580 14

In most cases, the diagnosis of systemic mastocytosis (SM) is based on histomorphologic evaluation of the bone marrow. We analyzed mast cell (MC) infiltration patterns in 57 cases of SM and 31 cases of mast cell hyperplasia (MCH). Tryptase immunohistochemical analysis was used for MC detection and CD25 to distinguish neoplastic from normal MCs. The following infiltration patterns were found: I, diffuse interstitial; II, focal, dense; III, focal, dense with an additional diffuse component, located preferentially around focal infiltrates; IV, focal, dense with an additional diffuse component evenly distributed throughout; and V, diffuse, dense. In 29 cases of MCH, MCs formed the type I pattern. The majority of SM cases exhibited patterns II to V; type IV was the most frequent (n = 36). Type V was seen in 3 cases of MC leukemia and 1 case of smoldering SM. In 1 case of SM, type I infiltration was found; the SM diagnosis was based on 3 minor SM criteria. Our data show that the infiltration pattern in SM correlates with the disease subtype and should be recognized as an important aspect in the histomorphologic evaluation of the bone marrow.
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PMID:Delineation of patterns of bone marrow mast cell infiltration in systemic mastocytosis: value of CD25, correlation with subvariants of the disease, and separation from mast cell hyperplasia. 1614 15


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