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

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).
Leuk Lymphoma 2004 Apr
PMID:Bone marrow mastocytosis associated with IgM kappa plasma cell myeloma. 1516 Sep 59

The study was performed on orchidectomized tissue and testicular biopsies sent for histopathological examination which included; 9 cases of orchitis, 6 pyocele, 9 haematocele, 13 seminomas, 5 embryonal cell carcinoma, 2 teratocarcinoma, 2 lymphoma, 4 yolk sac tumor, 17 infertility lesions and 6 normal. Toluidine blue stained sections were examined under high power magnification (hpm) and the number of mast cell present in 10 consecutive fields was counted. There was a considerable variation in the number and distribution of mast cells in various testicular lesions. Mast cells were observed mainly in the areas of inflammatory infiltrate, granulation tissue and immature fibrous tissue. In infertility, interstitium and tubular walls were the areas of predilection for the presence of mast cells. The highest number of mast cells was noted in infertility (23/hpm), compared to inflammatory/reactive lesions (19/hpm) and testicular neoplasms (2/hpm). The highest and the lowest mast cell concentration were observed in infertility and testicular tumours compared to inflammatory/reactive lesions, respectively. The role of mast cells in the pathogenesis of infertility and testicular tumourogenesis requires further investigation.
 ...
PMID:Mast cells in testicular lesions. 1550 26

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.
Leuk Lymphoma 2004 Nov
PMID:Aleukemic mast cell leukemia with abnormal immunophenotype and c-kit mutation D816V. 1551 20

Among the intestinal tumors of hematopoietic cell origin, lymphoma is the most common in the dog. Herein, we characterized the clinical and pathologic features of 11 dogs (average age, 10.6 +/- 2.5 years) with T-cell lymphoma of the intestinal tract with eosinophil infiltrates. No sex predominance was apparent. All had localized tumor masses in the small intestine. Grossly, the intestinal wall was thickened, and the lumen of the affected intestine was usually narrowed. Microscopically, we observed transmural diffuse invasion of round to pleomorphic tumor cells. Tumor cells showed varying morphology, from scanty to abundant cytoplasm, and round to ovoid nuclei with scattered to dense chromatin. In seven of the dogs, tumor cells had infiltrated into the epithelium. All showed infiltration of eosinophils and all 11 tumors had a T-cell phenotype (CD3+, CD79-). Only one tumor stained positive for the mast cell marker c-kit and none was positive for mast cell tryptase. We did not observe ultrastructurally apparent granules in any of the tumor cells. These results suggest that, in dogs, T-cell lymphomas of intestinal origin resemble mast cell tumors of intestinal origin with respect to cell structure and eosinophil infiltration. Therefore, in the absence of epitheliotropism, it is difficult to confirm the differential diagnosis without immunostaining for mast cell and lymphocyte markers, including mast cell tryptase, c-kit, CD3, and CD79.
 ...
PMID:T-cell lymphoma with eosinophilic infiltration involving the intestinal tract in 11 dogs. 1667 80

CD30 is a transmembrane protein selectively overexpressed on many human lymphoma cells and therefore an interesting target for antibody-based immunotherapy. However, binding of therapeutic antibodies stimulates a juxtamembrane cleavage of CD30 leading to a loss of target antigen and an enhanced release of the soluble ectodomain of CD30 (sCD30). Here, we show that sCD30 binds to CD30 ligand (CD153)-expressing non-target cells. Because antibodies bind to sCD30, this results in unwanted antibody binding to these cells via sCD30 bridging. To overcome shedding-dependent damage of normal cells in CD30-specific immunotherapy, we analyzed the mechanism involved in the release. Shedding of CD30 can be enhanced by protein kinase C (PKC) activation, implicating the disintegrin metalloproteinase ADAM17 but not free cytoplasmic calcium. However, antibody-induced CD30 shedding is calcium dependent and PKC independent. This shedding involved the related metalloproteinase ADAM10 as shown by the use of the preferential ADAM10 inhibitor GI254023X and by an ADAM10-deficient cell line generated from embryonically lethal ADAM10(-/-) mouse. In coculture experiments, the antibody-induced transfer of sCD30 from the human Hodgkin's lymphoma cell line L540 to the CD30-negative but CD153-expressing human mast cell line HMC-1 was inhibited by GI254023X. These findings suggest that selective metalloproteinase inhibitors blocking antibody-induced shedding of target antigens could be of therapeutic value to increase the specificity and reduce side effects of immunotherapy with monoclonal antibodies.
 ...
PMID:ADAM10 inhibition of human CD30 shedding increases specificity of targeted immunotherapy in vitro. 1721 Jul 15

Acral lick dermatitis ("lick granuloma") in dogs is often thought to have a behavioral etiology. However, other diseases may cause lesions on the distal legs, mimicking acral lick dermatitis. In this report, six dogs were presented with acral lick dermatitis-like lesions from different underlying causes-namely lymphoma, an orthopedic pin, deep pyoderma, mast cell tumor, leishmaniasis, and (presumptive) sporotrichosis.
 ...
PMID:Organic diseases mimicking acral lick dermatitis in six dogs. 1761 2

There is little quantitative information about the amount of fibrosis in lymphomas. The aim of the present study was to investigate the amount of fibrosis in lymphomas and to highlight the relationship between fibrosis and mast cells, the key players of fibrosis. Tissue sections of 60 patients with diagnosis of lymphoma were reevaluated for classification. The mean fibrotic-stained area percentage (F-SAP) was determined in van Gieson-stained digital images using image analysis (Mediscope, Dokuz Eylul University, Clinical Engineering, Turkey). Mast cells were visualized using streptavidin peroxidase immunohistochemistry with anti-tryptase staining. Twenty-seven (44%) cases were Hodgkin's lymphoma (HL). F-SAP was 11.09+/-8.96 and 1.72+/-1.76 for HL and non-HL cases (Mann-Whitney U, p<0.000), and the mean mast cell count (MMCC) was 24.63+/-13.58 and 8.03+/-8.07, respectively (Mann-Whitney U test, p<0.000). There was a significant difference between F-SAP and MMCC concerning different types of lymphomas (Kruskal-Wallis test, p>0.000). F-SAP was highest in nodular sclerosis HL, and MMCC was highest in mixed cellular HL. There was a strong positive correlation between MMCC and F-SAP (Pearson Correlation test, p<0.000, r=0.51). These results suggest that the amount of fibrosis demonstrates differences in subtypes of lymphomas, and mast cells are increased in fibrosing lymphomas. However, it seems likely that more than one cell type is involved.
 ...
PMID:Fibrosis in Hodgkin and non-Hodgkin lymphomas. 1780 76

Several reports of successful empirical treatment of idiopathic hypereosinophilic syndrome with imatinib led to the recent identification of the FIP1L1-PDGFRA fusion gene rearrangement, which characterizes a distinctive group of chronic eosinophilic leukemias. This fusion gene can be detected in eosinophils, neutrophils, mast cells, T cells, B cells and monocytes in FIP1L1-PDGFRA-positive hypereosinophilic patients suggesting a multilineage involvement. Furthermore, the same FIP1L1-PDGFRA rearrangement was identified in patients with hypereosinophilia and atypical mast cell proliferations, raising the question of a disease with two concomitant lines of differentiation. In addition, a recent report noted two cases with the association of FIP1L1-PDGFRA-positive chronic eosinophilic leukemia and T-cell lymphoblastic lymphoma (T-LBL). We report here the only third case of synchronous chronic eosinophilic leukemia and T-LBL, both associated with a FIP1L1-PDGFRA fusion transcript, confirming the occurrence of such disease and suggesting a clonal proliferation with two lines of differentiation probably arising from a primitive multipotent medullary stem cell.
 ...
PMID:Synchronous FIP1L1-PDGFRA-positive chronic eosinophilic leukemia and T-cell lymphoblastic lymphoma: a bilineal clonal malignancy. 1802 20

Multiple myeloma oncogene 1/interferon regulatory factor 4 (MUM1/IRF4) is involved in lymphoid cell differentiation, particularly in the production of plasma cells. We examined the immunoreactivity of mouse monoclonal antibody Mum-1p to MUM1/IRF4 and compared it with expression of CD79a and CD20 in 109 plasmacytomas in 107 dogs. Tissues had been fixed in formalin and embedded in paraffin. One hundred one of 109 (93.5%) tumors were positive for MUM1/IRF4. The staining was nuclear with weak cytoplasmic reaction. Fifty-nine of 105 (56.2%) plasmacytomas were positive for CD79a; only 21 of 108 (19.4%) cases were positive for CD20. MUM1/IRF4 staining was performed on 139 other tumors including B- and T-cell lymphomas, histiocytic proliferations, mast cell tumors, and melanocytic tumors. The only MUM1/IRF4-positive nonplasmacytic tumors were 10 B-cell lymphomas and 1 anaplastic lymphoma. We conclude the following: 1) Antibody Mum-1p is very specific for canine plasmacytomas, 2) antibody Mum-1p is superior in sensitivity and specificity to CD79a and CD20 for the identification of canine plasmacytomas in formalin-fixed, paraffin-embedded tissues, 3) canine lymphomas that express MUM1/IRF4 are few and usually of B-cell origin, 4) other canine leukocytic and melanocytic tumors do not express MUM1/IRF4, and 5) prospective studies are needed to determine whether the expression of MUM1/IRF4, particularly in lymphomas, has prognostic significance.
 ...
PMID:Immunohistochemical detection of multiple myeloma 1/interferon regulatory factor 4 (MUM1/IRF-4) in canine plasmacytoma: comparison with CD79a and CD20. 1803

Flow cytometric immunophenotyping remains an indispensable tool for the diagnosis, classification, staging, and monitoring of hematologic neoplasms. The last 10 years have seen advances in flow cytometry instrumentation and availability of an expanded range of antibodies and fluorochromes that have improved our ability to identify different normal cell populations and recognize phenotypic aberrancies, even when present in a small proportion of the cells analyzed. Phenotypically abnormal populations have been documented in many hematologic neoplasms, including lymphoma, chronic lymphoid leukemias, plasma cell neoplasms, acute leukemia, paroxysmal nocturnal hemoglobinuria, mast cell disease, myelodysplastic syndromes, and myeloproliferative disorders. The past decade has also seen refinement of the criteria used to identify distinct disease entities with widespread adoption of the 2001 World Health Organization (WHO) classification. This classification endorses a multiparametric approach to diagnosis and outlines the morphologic, immunophenotypic, and genotypic features characteristic of each disease entity. When should flow cytometric immunophenotyping be applied? The recent Bethesda International Consensus Conference on flow cytometric immunophenotypic analysis of hematolymphoid neoplasms made recommendations on the medical indications for flow cytometric testing. This review discusses how flow cytometric testing is currently applied in these clinical situations and how the information obtained can be used to direct other testing.
 ...
PMID:Flow cytometric immunophenotyping for hematologic neoplasms. 1819 45


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>