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)

Stem cell factor receptor (SCFR, c-kit), normally expressed on haematopoietic and mast cells, plays a regulatory role in cellular growth and differentiation. Dysregulated expression of SCFR may contribute to neoplastic transformation. We investigated expression of SCFR on malignant canine mast cells obtained directly from spontaneous canine mast cell neoplasms, in an attempt to determine whether these undifferentiated cells maintained expression of this growth-promoting cytokine receptor. Malignant mast cells (histological grade 2) from skin tumours or lymph node metastases were collected from canine patients, and SCFRs were detected by flow cytometric analysis of these cells. All of the tumours bound mouse and canine recombinant stem cell factor (SCF), indicating that the cells not only expressed SCFRs, but that the receptors possessed the functional property of ligand binding. Immunoglobulin Fc receptors for canine IgE were identified on these cells by flow cytometry, a further indication that the cells analysed were mast cells and retained some differentiated features. Immunohistochemical analysis of formalin-fixed, paraffin wax-embedded mast cell tumour biopsies confirmed expression of SCFRs by malignant cells from each tumour. The relative binding of SCF to suspensions of tumour cells, as assessed by flow cytometry, correlated with the intensity of immunolabelling for SCFR in sections of the same tumours, suggesting variability in SCFR expression between tumours. Agarose gel electrophoresis of the products of SCFR reverse transcription-polymerase chain reaction derived from each tumour had the molecular weight predicted for canine SCFR cDNA on the basis of the mouse and human counterparts. This further confirmed SCFR expression by malignant canine mast cells. Taken together, these results show that a membrane receptor capable of triggering cell growth is expressed by malignant canine mast cells, suggesting a role for this receptor in the aetiology of canine mast cell cancer. This relatively common malignancy of the dog would seem to present an opportunity for the investigation of the potential role of the SCF/SCFR pathway in the development of spontaneous malignancies of mast cells.
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PMID:Expression of stem cell factor receptor (c-kit) by the malignant mast cells from spontaneous canine mast cell tumours. 900 81

The case of a 62-year-old man who presented with acute abdominal pain and a widespread tumor involving the retroperitoneum is described. Three weeks after initial presentation, the patient died suddenly of acute cardiac failure with signs of arrhythmia. Autopsy revealed a disseminated tumor with infiltration of the retroperitoneal fat, as well as nodules in the left testis and the right atrium. The tumor cells were reactive for CD45, vimentin, and chloroacetate esterase, but were unreactive with a broad spectrum of antibodies against myelomonocytic and lymphocytic antigens and with antibodies against tryptase and c-kit (CD117), which are characteristic markers for mast cells. However, the bone marrow exhibited the typical picture of mastocytosis, with disseminated clusters of differentiated spindle-shaped cells that stained strongly for tryptase, c-kit, and chloroacetate esterase. No infiltrates of well-differentiated mastocytosis could be detected in any of the extramedullary tissues investigated. A diagnosis of bone marrow mastocytosis with an associated undifferentiated extramedullary tumor of hemopoietic origin was established. By definition, the extramedullary tumor could not be diagnosed as a granulocytic sarcoma or (differentiated) mastocytoma, but the possibility that a mast cell progenitor could be involved in the evolution of both tumors cannot be ruled out.
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PMID:Bone marrow mastocytosis associated with an undifferentiated extramedullary tumor of hemopoietic origin. 914 Mar 15

The immunophenotypic characteristics of both bone marrow (BM) and peripheral blood (PB) mast cells (MC), from a patient suffering from an aggressive systemic mast cell disease (SMCD), were sequentially analyzed by flow cytometry using direct immunofluorescence. Analysis was carried out at diagnosis, during clinical response induced by interferon alfa-2h/prednisone therapy, and later at relapse. Our results show that together with the CD117 and IgE characteristic markers, at diagnosis BM MC showed strong expression of CD11c, CD13, CD29, CD33, CD44, CD45, CD63, and CD71, and they were also positive for CD2, CD22, CD25, and CD54 although at a lower level. PB MC displayed similar immunophenotypic characteristics although they had a lower expression of CD11c, CD25, CD33, CD63, CD69, and CD71 with a higher reactivity for CD117. Unlike BM MC, PB MC were weakly positive for CD41a and CD61. Sequential studies showed decreased numbers of both BM and PB MC during clinical response associated with a higher expression of the CD29 and CD54 adhesion molecules. In turn, clinical relapse was related to increased numbers of PB and BM MC together with lower CD2, CD11c, CD45, and and CD54 expression and a higher reactivity for the CD117 and CD25 antigens. CD2 had become negative at the last follow-up study. In addition, an increased proportion of S-phase MC was observed at relapse. These findings suggest that the assessment of the quantitative expression of cell-adhesion molecules and growth-factor receptors together with cell cycle studies of mast cells could be of value for monitoring therapy and predicting clinical outcome in aggressive SMCD.
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PMID:Sequential immunophenotypic analysis of mast cells in a case of systemic mast cell disease evolving to a mast cell leukemia. 914 16

The case of a 63-year-old man with a widespread retroperitoneal tumor and two tumor nodules in the left testis is described. Histopathological and cytopathological examination of tissue from the retroperitoneal tumor led to a diagnosis of lymphoreticular neoplasia. The patient died in acute cardiac failure, five weeks after initial presentation. Autopsy revealed another tumor nodule in the right atrium. Macroscopically, the bone marrow appeared normal. The tumor cells were reactive for CD45, vimentin and chloroacetate esterase, but were uncreative with a broad spectrum of antibodies against myelomonocytic and lymphocytic antigens and antibodies against tryptase and c-kit (CD117), characteristic markers for mast cells. However, the bone marrow exhibited the typical picture of mastocytosis. A diagnosis of bone marrow mastocytosis with an associated secondary extramedullary mast cell sarcoma was established. The cause of death was heart failure due to arrhythmia caused by an exophytic atrioseptal tumor nodule.
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PMID:[Association of bone marrow mastocytosis with extremely immature extramedullary mast cell sarcoma]. 927 45

The aim of the present study was to explore the diagnostic value of the immunophenotypic analysis of bone marrow mast cells (BMMC) in indolent systemic mast cell disease (SMCD) patients. For that purpose, a total of 10 SMCD patients and 19 healthy controls were analyzed. Our results show that BMMC from SMCD are different from normal BMMC with regard to both their light scatter and immunophenotypic characteristics. Accordingly, forward light scatter (FSC), side (90 degrees) light scatter (SSC), and baseline autofluorescence levels were higher in BMMC from indolent SMCD patients than they were in control subjects. From the immunophenotypic point of view, the most striking findings were the constant expression of CD2 (P = .0001), CD25 (P = .0001), and CD35 (P = .06) molecules by BMMC from SMCD patients, markers that were absent from all normal controls. In contrast, CD71, absent in BMMC from indolent SMCD, was positive in BMMC from normal subjects. Although, slight differences between BMMC from SMCD patients and normal controls were found in several other markers, they did not reach statistical significance. In conclusion, our results show that simultaneous assessment of FSC/SSC and reactivity for the CD117, CD2, CD25, CD33, and CD35 forms the basis for the immunophenotypic characterization of BMMC from SMCD in adults and should be integrated with clinical and morphologic studies for the diagnosis of the disease.
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PMID:Indolent systemic mast cell disease in adults: immunophenotypic characterization of bone marrow mast cells and its diagnostic implications. 953 82

The c-kit gene product (CD117) is known to be expressed by a variety of normal human tissue cell types, including breast epithelium, germ cells, melanocytes, immature myeloid cells, and mast cells. To further characterize the expression of this antigen, 117 normal human tissues and 576 human tumors were studied by paraffin section immunohistochemistry. Varying degrees of CD117 expression were identified in various normal cells and in 53% of all tumors studied. In most cases (42% of total), CD117 expression was weak. Expression was most common in mast cell disease (100%), testicular germ cell tumors (100%), endometrial carcinomas (100%), papillary and follicular thyroid carcinomas (100%), small cell carcinomas (91%), malignant melanomas (90%), and ovarian epithelial carcinomas (87%). Strong immunoreactivity was only identified in cases of mast cell disease (11 of 11 cases), serous ovarian carcinoma (3 of 16), malignant melanoma (2 of 40), small cell lung carcinoma (one of seven), and adenoid cystic carcinoma (one of one). Although the pattern of reactivity was primarily cytoplasmic, a membrane staining pattern was seen in a subset of cases, and strong membrane staining was identified in normal mast cells and all cases of mast cell disease. The lack of tumor specificity of weak expression of this antigen limits its diagnostic utility in most cases. However, the strong membrane reactivity for CD117 identified in mast cells may be useful in the diagnosis of mast cell disorders.
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PMID:Paraffin section detection of the c-kit gene product (CD117) in human tissues: value in the diagnosis of mast cell disorders. 959 74

We have developed a method to purify mast cells from enzymatic isolates of human colonic mucosa (HCM) and submucosa/muscle (HCS), and gastric mucosa (HGM) and submucosa/muscle (HGS). The purification of mast cells from these enzymatic isolates involves positive affinity-magnetic selection of mast cells using a monoclonal antibody specific for the c-kit receptor tyrosine kinase (CD117). The monoclonal antibody is coupled to Dynabeads for positive affinity selection of c-kit receptor positive cells which includes mast cells. This selection procedure generates preparations of mast cells from HCM, HCS, HGM and HGS that are 80% pure. The purified mast cells were microscopically normal and viable (> 85%). The functionality of purified mast cells was examined by studying the effect of anti-human IgE, Concanavalin A (Con A) and calcium ionophore A23187 on histamine release. These results show that this purification procedure generates microscopically normal, viable and functional mast cells. This method of purifying human gastrointestinal tissue mast cells may be a valuable tool for the further study of mast cell heterogeneity and the role of mast cells in the gastrointestinal tract.
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PMID:Purification of human colonic and gastric mast cells. 969 66

The primary role of protooncogene c-kit in mast cell differentiation is supported by the development of mast cells from CD34+/CD117+(c-kit) myeloid precursors. Growth factor independence, neoplastic transformation and differentiation of mast cells were found in association with c-kit activating mutations in both murine and human mastocytoma and mast cell diseases. We have identified a novel c-kit mutation (D816Y) in peripheral blood mononuclear cells from a patient with AML (M2), massive presence of mast cells in bone marrow and rapid progression of the disease. The mutation, a G-->T transversion at nt 2467 of the c-kit gene resulting in Asp816-->Tyr substitution, corresponds to the D814Y and D817Y mutations identified and characterized in the murine P815 mastocytoma and the rat RBL-2H3 mast cell leukemia cell lines. The absence of SCF transcripts that we found by RTPCR in the patient's blasts indicates that, also in humans, this activating mutation leads to SCF independent growth. The expression of the mutant allele on Kit signaling may be further enhanced by trisomy of chromosome 4 (carrying the c-kit gene) in the patient's blasts. From these findings it is concluded that mast cells could be generated from a leukemic CD34/CD117-positive clone, that combines the antigenic expression of mast cell precursor to the growth and differentiation factor-independence which was derived by the c-kit D816Y mutation.
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PMID:In vivo differentiation of mast cells from acute myeloid leukemia blasts carrying a novel activating ligand-independent C-kit mutation. 971 3

A subset of patients with systemic mastocytosis (SM) develop acute myeloid leukaemia (AML). However, little is known about the biology of such leukaemias and their relationship to the mast cell (MC) lineage. We report on two female patients who suffered from SM and AML. According to FAB criteria, the leukaemias were classified as AML-M4 (patient 1) and AML-MO (patient 2). The coexistence of the two distinct neoplasms (AML and SM) was demonstrable by immunostaining of serial bone marrow (BM) sections with monoclonal antibodies (mAb). In particular, the MC infiltrates were found to react with mAb against MC-tryptase and MC growth factor receptor c-kit (CD117), but not with mAb to CD15 or CD34. In contrast, the AML blasts were immunoreactive for CD15 (patient 1) or CD34 (patient 2), but did not express tryptase. The c-kit point mutation Asp-->Val at codon 816, considered to play a role in the transformation of MC progenitors, was detected in patient 1 in a BM cell fraction containing 4% MC. However, no c-kit mutation was found in pure AML blasts (<1% MC). These findings argue against an evolution of the AML clone from neoplastic MC or MC-committed progenitors.
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PMID:Systemic mastocytosis associated with acute myeloid leukaemia: report of two cases and detection of the c-kit mutation Asp-816 to Val. 985 25

IL-4 is central to the formation of IgE and the development of Th2 effector cells, both key features of an allergic response. We have examined IL-4 production early in the formation of an allergic response by using a previously established human in vivo model of allergic rhinitis where allergic subjects are challenged internasally with allergen and the particulate pollutant diesel exhaust particles (DEP). This model is characterized by enhanced IgE production and deviation to a Th2-type cytokine profile in nasal lavage fluid from these subjects. In this model, IL-4 protein and IL-4-positive cells could first be detected 4 h after challenge and maximal production was observed after 18 h. Two-color flow cytometric analysis for the detection of intracellular IL-4 and surface markers was performed on nasal cells recovered 4 h after challenge. At this time, CD117(+) (c-kit+) cells constituted between 65 and 100% of the IL-4(+) cells, while 0-12% of the IL-4(+) cells were CD3 positive. No IL-4(+) CD19/CD20(+) or IL-4(+) CD56(+) cells were detected at 4 h. As the allergic response progressed the primary source of IL-4 changed. At the peak of IL-4 production, 18 h after challenge, CD3(+) comprised the majority of cells staining for intracellular IL-4 (73 to 100%). Thus we show an initial role for cells of the mast cell/basophil lineage residing in the nasal mucosa in the initial production of IL-4, which frames the subsequent immune response by expanding the repertoire of TH2 cytokine-producing cells in the local microvicinity.
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PMID:Early IL-4 production driving Th2 differentiation in a human in vivo allergic model is mast cell derived. 988 52


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