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)

Hodgkin's lymphoma (HL) is characterized by a few Hodgkin, Reed-Sternberg cells (HRS) surrounded by benign cells. We recently reported that mast cells were the predominant CD30L-positive cells in HL tumours, and that they activate HRS in vitro through CD30L-CD30 interaction. Here, we investigated the clinical importance of mast cell infiltration in the tumours of 123 patients. Tumour specimens were stained with a mast-cell-specific antibody that detects tryptase. Mast cells were detected in virtually every case and increasing numbers of mast cells correlated to nodular sclerosis histology (P = 0.008). Patients with higher mast cell infiltration had a worse relapse-free survival (P = 0.01).
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PMID:Mast cell infiltration correlates with poor prognosis in Hodgkin's lymphoma. 1235 14

The principles of the new WHO classification of haematopoietic and lymphoid tumours are based on those defined in the Revised European American classification of Lymphoid neoplasms (REAL), published by the International Lymphoma Study Group (ILSG) in 1994. Thus, the new WHO classification may be considered an updated version of the REAL classification rather than of the old WHO classification published in 1976. Disease entities are defined on the basis of morphological, phenotypic, genotypic, and clinical data. The relative impact of these characteristics varies among different diseases and there is "no gold standard". Thus, the strict hierarchy among diagnostic criteria, headed by morphology and followed by immunohistochemistry and genetics, has been discontinued. The WHO classification not only encompasses lymphoid tumours but extends to myeloid, mast cell and histiocytic/dendritic cell malignancies. Neoplasms are primarily stratified according to their tumour cell lineage. For each neoplasm a cell of origin is postulated. The classification of lymphoid malignancies recognises three major categories, B-cell neoplasms, T-/NK-cell neoplasms, and Hodgkin lymphomas. B-cell and T-cell lymphomas are further divided into precursor neoplasms and mature neoplasms, the latter being subdivided according to their clinical manifestation into disseminated/leukaemic, extranodal and nodal malignancies. In contrast to previous classifications, the neoplasms are grouped neither according to their histological grade (Kiel classification) nor according to their clinical aggressiveness (International Working Formulation). However, the histological grade is considered a prognostic factor which enters into the description of each disease entity. Hodgkin's disease, now more appropriately termed Hodgkin lymphoma, comprises nodular lymphocyte-predominant Hodgkin lymphoma and classical Hodgkin lymphomas of nodular sclerosis, mixed cellularity, lymphocyte-depleted and lymphocyte-rich subtype. For practical purposes this minireview disregards the description of myeloid, macrophage/histiocytic, dendritic cell and mast cell disorders. Furthermore, the present paper is restricted to those lymphoid tumours that are not already identically described in the REAL classification, in order to focus on what is really new in the WHO classification.
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PMID:Who is WHO and what was REAL? 1258 44

The new WHO classification is based on the principles of REAL classification of lymphoma and expands to myeloid, mast cell and histiocytic/dendritic neoplasms. The distinct diseases are defined according to a combination of morphology, immunophenotype, genetic features, and clinical syndromes, and the cell origin is postulated. Lymphatic leukemia is included in lymphoma. The lymphoid malignancies are grouped into B cell lymphoma, T/NK cell lymphoma and Hodgkin lymphoma, and the myeloid neoplasm are grouped into 4 categories; chronic myeloproliferative diseases(chronic myelogeneous leukemia, polycythemia vera, chronic idiopathic myelofibrosis, essential thrombocythemia etc.), myelodysplastic/myeloproliferative diseases (chronic myelomonocytic leukemia, juvenile myelomonocytic leukemia etc.), myelodysplastic diseases(perfactory anemia, refractory anemia with ringed sideroblasts etc.) and acute myeloid leukemia.
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PMID:[Malignant lymphoma and leukemia concepts in new WHO classification]. 1367 44

Hodgkin lymphoma (HL) is characterised histologically by a minority of malignant Hodgkin and Reed-Sternberg (HRS) cells surrounded by benign cells, and clinically by a relatively good prognosis. The treatment, however, leads to a risk of serious side effects. Knowledge about the biology of the disease, particularly the interaction between the HRS cells and the surrounding cells, is essential in order to improve diagnosis and treatment. HL patients with abundant eosinophils in the tumours have a poor prognosis, therefore the eosinophil derived protein eosinophil cationic protein (ECP) was studied. Serum-ECP (S-ECP) was elevated in most HL patients. It correlated to number of tumour eosinophils, nodular sclerosis (NS) histology, and the negative prognostic factors high erythrocyte sedimentation rate (ESR) and blood leukocyte count (WBC). A polymorphism in the ECP gene (434(G>C)) was identified and the 434GG genotype correlated to NS histology and high ESR. The poor prognosis in patients with abundant eosinophils in the tumours has been proposed to depend on HRS cell stimulation by the eosinophils via a CD30 ligand (CD30L)-CD30 interaction. However, CD30L mRNA and protein were detected in mast cells and the predominant CD30L expressing cell in HL is the mast cell. Mast cells were shown to stimulate HRS cell lines via CD30L-CD30 interaction. The number of mast cells in HL tumours correlated to worse relapse-free survival, NS histology, high WBC, and low blood haemoglobin. Survival in patients with early and intermediate stage HL, diagnosed between 1985 and 1992, was generally favourable and comparatively limited treatment was sufficient to produce acceptable results for most stages. The majority of relapses could be salvaged. Patients treated with a short course of chemotherapy and radiotherapy had an excellent outcome. In conclusion prognosis is favourable in early and intermediate stages and there are possibilities for further improvements based on the fact that mast cells and eosinophils affect the biology and prognosis of HL.
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PMID:Bystander cells and prognosis in Hodgkin lymphoma. Review based on a doctoral thesis. 1550 24

Mast cells are involved in many disorders where the triggering mechanism that leads to degranulation and/or cytokine secretion has not been defined. Several chronic inflammatory diseases are associated with increased mast cell numbers and upregulation of the TNF receptor family member CD30, but the role of elevated CD30 expression is poorly understood. Here we report what we believe to be a novel way to activate mast cells with CD30 that leads to degranulation-independent secretion of chemokines. CD30 induced a de novo synthesis and secretion of the chemokines IL-8, macrophage inflammatory protein-1alpha (MIP-1alpha), and MIP-1beta, a process involving the MAPK/ERK pathway. Mast cells were found to be the predominant CD30 ligand-positive (CD30L-positive) cell in the chronic inflammatory skin diseases psoriasis and atopic dermatitis, and both CD30 and CD30L expression were upregulated in lesional skin in these conditions. Furthermore, the number of IL-8-positive mast cells was elevated both in psoriatic and atopic dermatitis lesional skin as well as in ex vivo CD30-treated healthy skin organ cultures. In summary, characterization of CD30 activation of mast cells has uncovered an IgE-independent pathway that is of importance in understanding the entirety of the role of mast cells in diseases associated with mast cells and CD30 expression. These diseases include Hodgkin lymphoma, atopic dermatitis, and psoriasis.
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PMID:Mast cell CD30 ligand is upregulated in cutaneous inflammation and mediates degranulation-independent chemokine secretion. 1696 9

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.
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PMID:ADAM10 inhibition of human CD30 shedding increases specificity of targeted immunotherapy in vitro. 1721 Jul 15

Systemic mastocytosis is a disease characterized by multifocal mast cell proliferation in the bone marrow or other extracutaneous organs. Because of loosely scattered and hypo-/agranular mast cells, the diagnosis is sometimes very difficult. In the bone marrow, mast cell infiltration may be associated with prominent lymphoid infiltration leading to a misdiagnosis of a low grade non-Hodgkin lymphoma. A 49-year-old woman presented with right arm and leg pain, psychiatric symptoms, and diarrhea for four years. Physical examination and laboratory investigation revealed hepatosplenomegaly, anemia, mild thrombocytosis, mild leucocytosis and lymphocytosis. In the bone marrow biopsy, there was a prominent B lymphocyte proliferation reminiscent of a low grade non-Hodgkin lymphoma/leukemia and there were some spindle cells aggregates in paratrabecular location. The consecutive bone marrow biopsies were similar to the first. The subsequent splenectomy specimen exhibited striking fibrosis. In the lymph node sections, there was marginal zone hyperplasia. Multifocal accumulations of mast cells were strongly positive with mast cell tryptase and CD117 on immunohistochemical staining, though no metachromasia was identified in Giemsa and Toluidine Blue stained aspirates and tissue sections, probably due to hypo-/agranulation of mast cells. The case was presented to emphasize the importance of the antibody to mast cell tryptase in the diagnosis of mastocytosis and to discuss problems of differential diagnosis of systemic mastocytosis.
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PMID:Systemic mastocytosis presenting with a prominent B lymphocyte proliferation in the bone marrow and extensive fibrosis of the spleen. 1747 86

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.
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PMID:Fibrosis in Hodgkin and non-Hodgkin lymphomas. 1780 76

The composition of reactive cell populations, which constitute the majority of tumor load in Hodgkin's lymphoma (HL), can influence the prognosis of the disease. Besides widely accepted and applied prognostic scores, the authors evaluate biological factors that may have a prognostic impact. Previous data indicate that the rate of eosinophils and mast cells in the reactive cell population, determined already at diagnosis, can be used for this purpose. Histological samples from 104 patients with HL with an average follow-up period of 110 (24-214) months were retrospectively analyzed. Mast cell positivity was associated with better overall survival, although this difference was only of borderline statistical significance (p=0.092). No significant difference was found in parameters like overall survival (OS, p=0.906) or event-free survival (EFS, p=0.307) of eosinophil-positive vs. -negative cases or in EFS (p=0.742) of mast cell-positive vs. -negative individuals (criterion for a positive specimen was more than 5% of appropriate cells in the reactive cell population). Looking at the effect of eosinophilia and mastocytosis together, there was no significant difference between the subgroups categorized according to the combined presence of the two cell types. It seems that tissue eosinophil and mast cell predominance have no prognostic value that could be used in clinical practice, although a tendency for correlation of mast cell positivity with overall survival could be seen. For a definitive statement, multicenter studies should be performed involving a higher number of patients suffering from HL.
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PMID:Retrospective analysis of the prognostic role of tissue eosinophil and mast cells in Hodgkin's lymphoma. 1792 53

Diagnosis of systemic mastocytosis (SM) is mainly based on the morphological demonstration of compact mast cell infiltrates in various tissue sites. In almost all patients such infiltrates are detected in the bone marrow. Reliable immunohistochemical markers for the diagnosis and grading of SM have been established, but various differential diagnoses including myeloproliferative neoplasms, basophilic and eosinophilic leukemias may be very difficult to delineate. Even more challenging is the recognition of hematological neoplasms with signs of mast cell differentiation but not fulfilling diagnostic criteria for SM, especially the rare myelomastocytic leukemia. It is also important to separate the reactive state of mast cell hyperplasia from indolent variants of SM, especially those with a very low degree of bone marrow infiltration and absence of compact mast cell infiltrates. When the lymphocytic component of the SM infiltrate is very prominent, SM may be confused with an indolent lymphoma, especially lymphoplasmacytic lymphoma which almost always shows a marked reactive increase in mast cells. In aggressive and leukemic variants of SM, mast cells may be very atypical and devoid of metachromatic granules. This hypogranulation can be regarded as cellular atypia and may lead to the misdiagnosis aspect of monocytic leukemia or histiocytic neoplasm. Regarding immunohistochemical anomalies, mast cells in aggressive and leukemic SM have been found to express CD30 (Ki1-antigen). Thus, anaplastic large cell lymphoma or Hodgkin's disease may first be considered rather than SM. There is increasing evidence that most patients with long-standing adult-type urticaria pigmentosa-like skin lesions have in fact indolent SM. Therefore, such skin lesions are an important clue to the correct diagnosis in these patients. However, in aggressive or leukemic SM skin lesions are usually absent and then the correct diagnosis relies on an appropriate investigation of bone marrow biopsy specimens using both SM-related immunohistochemical markers (tryptase, KIT, CD25, CD30) but also markers excluding potential differential diagnoses. Investigation for presence of the activating KIT point mutation D816V is very helpful to establish a correct diagnosis of SM in all the difficult cases exhibiting a low degree of bone marrow infiltration or puzzling morphological findings.
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PMID:Differential diagnoses of systemic mastocytosis in routinely processed bone marrow biopsy specimens: a review. 2061 12


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