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)

Human mast cells and basophil granulocytes can be easily recognized in normal tissues by light microscopy. In one mast cell and one basophilic leukemic case considered in this study, mast cells and basophils were morphologically quite similar and could not therefore be clearly defined merely by their morphological features. Both types of cells showed round nuclei and deep purple granules. The diagnosis of mast cell leukemia or basophilic leukemia was made on the basis of different cytochemical patterns. In the case of mast cell leukemia, peroxidase and PAS stains were negative, while chloroesterase was strongly positive; in the case of basophilic leukemia, peroxidase and PAS stains were positive, while chloroesterase reaction showed a peculiar pattern. Toluidine blue metachromasia and astra blue positivity were present in the cells of both cases.
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PMID:Mast cell leukemia and acute basophilic leukemia. Cytochemical studies. 74 30

Passive immunotherapy was attempted in a patient with mast cell leukemia using antibody against IgE. The results of both in vitro and in vivo studies indicate that although receptor sites for IgE were retained by the malignant mast cell, a secretory defect was present characterized by the spontaneous release of histamine and an impaired secretory response to anti-IgE antibody. Anti-IgE antibody selectively and reproducibly reduced the number of circulating mast cells probably by facilitating their permanent uptake by the reticuloendothelial system. Tolerance was not achieved with high dose deaggregated sheep IgG, nor were we able to confirm the effectivity of immunochemotherapy based on linking chlorambucil to antibody directed against the tumor-associated "antigen" IgE.
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PMID:An approach to immunotherapy using antibody to IgE in mast cell leukemia. 108 94

The mast cell, equipped with enzymes, chemotactic factors, a vasoactive amine, an anticoagulant, and lipid-derived proinflammatory products, may be essential in tissue modeling as well as in defense. Its primarily perivascular location in skin and the mucosa of the respiratory tract and the gut assures its availability to counter parasites. By the same token, the mast cell is responsible for interactions with inhaled, ingested, and injected antigens that comprise IgE-mediated allergic reactions. Abnormally high numbers of mast cells in the skin, either localized or generalized, result in urticaria pigmentosa or generalized cutaneous mastocytosis, respectively. Tissue infiltration by excessive mast cells, primarily in gut, bone, liver, and spleen, results in systemic mastocytosis; this may be accompanied by myelodysplasia or lymphoma and may eventuate in mast cell leukemia. Until the etiology of mastocytosis is understood, the treatment is symptomatic: histamine antagonism by H1 +/- H2 blockade for flushing, itching, and gastric distress; cyclooxygenase inhibition to prevent prostaglandin D2 (PGD2)-induced hypotension when indicated; and oral cromolyn to prevent gastrointestinal symptoms and bone pain.
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PMID:Mast cell disease. 149 Jun 22

The neutral protease tryptase has been isolated from a human mast cell line, HMC-1. The HMC-1 line was established from the peripheral blood of a patient with mast cell leukemia and maintained as continuously proliferating clones in vitro and as solid mast cell tumors in nude mice. HMC-1-derived tryptase was purified by sequential chromatography on Dowex 1, DEAE 5 PW, and heparin-agarose. Purified tryptase has an apparent molecular weight of 150,000, as determined by molecular sieve HPLC, but migrates as a doublet of bands of 32/35,000 on SDS-PAGE gels. Maximal enzymatic activity was observed at pH 8.5. Cleavage of tosyl-L-arginine methyl ester by purified tryptase was inhibited by dansyl-L-glutamyl-glycyl-L-arginine chloromethyl ketone 2 HCl, HgCl2, tosyl-L-lysine chloromethyl ketone, leupeptin, and PMSF but not by benzamidine, aprotinin, tosyl-L-phenyl-alanine chloromethyl ketone, soybean trypsin inhibitor, human plasma, ovomucoid inhibitor, or lima bean trypsin inhibitor. Microsequencing of purified tryptase yielded an amino terminal sequence that was identical to that previously reported for human pituitary-derived tryptase.
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PMID:Purification of tryptase from a human mast cell line. 211 May 91

A case of malignant mastocytosis with peripheral blood involvement is presented. The course of the patient's illness was complicated by recurrent hypotensive episodes, presumed to have been caused by mast cell degranulation. Treatment with hydroxyurea was associated with persistent hypotension which resulted in death. It has been proposed that the diagnosis of mast cell leukemia be given to patients presenting with greater than 10% atypical mast cells in the blood. However, review of 16 published cases of malignant mastocytosis with circulating mast cells reveals that the clinical manifestations, complications, and survival do not vary significantly with the percentage of peripheral blood mast cells. Patients with malignant mastocytosis with significant involvement by atypical mast cells in the bone marrow and peripheral blood should be considered as having an aggressive disease, regardless of the percentage of circulating mast cells.
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PMID:Malignant mastocytosis with circulating mast cells. 171 11

We report the clinical and pathologic findings in one case of mast cell leukemia observed in a series of 60 patients with systemic mast cell disease. The leukemic variant of systemic mast cell disease is rapidly fatal (mean duration of survival, less than 6 months) in contrast to most nonleukemic cases, which follow an indolent clinical course. On the basis of our case and eight previously reported cases, mast cell leukemia is characterized by a substantial increase in atypical mast cells in the peripheral blood, diffuse infiltration with atypical mast cells in the bone marrow, a strong association with peptic ulcer disease, prominent constitutional symptoms, and hepatosplenomegaly. These cases should be distinguished from malignant mastocytosis without a substantial number of circulating atypical mast cells and also cases of acute nonlymphocytic leukemia that arise in the background of systemic mast cell disease.
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PMID:Mast cell leukemia: report of a case and review of the literature. 309 98

The neoplastic proliferation of tissue mast cells constitutes a group of rare diseases that have localized and systemic variants. The cytologic (n = 7) and histologic (n = 38) findings in bone marrow from a total of 45 patients with systemic mastocytosis were evaluated. Three distinct histologic patterns of marrow involvement were distinguished. In 21 cases a patchy or focal infiltration pattern was encountered. Mast cell aggregates were located predominantly in peritrabecular and perivascular areas. The adjacent trabeculae were thickened. A dense network of reticulin fibers and foci of lymphocytes accompanied the mast cell infiltrates. Increased numbers of eosinophils frequently demarcated the mast cell infiltrates from the surrounding tissue. In the noninfiltrated marrow areas hematopoiesis and the distribution of fat cells appeared to be normal. This histologic pattern, designated type 1, was observed exclusively in patients showing primary involvement of the skin, indistinguishable from urticaria pigmentosa. In 14 additional cases peritrabecular and perivascular sheets of mast cells, with concomitant fibrosis and osteosclerosis, were also present. Unlike the findings in type 1, however, the noninfiltrated marrow areas showed marked reductions in fat cell content and markedly increased granulocytopoiesis or increased numbers of blast cells (infiltration pattern type 2). On the basis of the hematologic and clinical findings, chronic myeloid leukemia was diagnosed in six of these cases, myelomonocytic leukemia in three cases, and acute myeloid leukemia in two cases. The bone marrow of three patients was diffusely infiltrated by atypical mast cells, leading to marked hypoplasia of fat cells and blood cell precursors. These histologic features were identified as infiltration pattern type 3. The diagnosis of mast cell leukemia was confirmed in all three cases by the presence of numerous mast cells in the blood. The prognosis for patients with the type 1 marrow infiltration pattern and primary skin involvement was favorable (actuarial survival rate five years after diagnosis, 0.75). This variant was called benign systemic mastocytosis. Primary skin involvement did not occur in the patients with type 2 or 3 infiltration patterns. The prognosis for these patients was poor (actuarial survival five years after diagnosis, 0.17 for type 2 and 0.00 for type 3). These two forms were accordingly designated malignant systemic mastocytosis.
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PMID:Bone marrow findings in systemic mastocytosis. 386 Apr 69

The c-kit proto-oncogene encodes a receptor tyrosine kinase that is known to play a crucial role in mast cell growth and differentiation. In a human mast cell leukemia cell line (HMC-1), KitR was found to be constitutively phosphorylated on tyrosine, activated and associated with phosphatidylinositol 3-kinase (P13K) in the absence of autocrine production of SCF. Sequencing of c-kit cDNA revealed that c-kit genes of HMC-1 cells were composed of a normal, wild-type allele and a mutant allele with two point mutations in codon 560 and codon 816, resulting in intracellular amino acid substitutions of Gly-560 for Val and Val-816 for Asp, respectively. Murine c-kit mutants encoding Gly-559 and/or Val-814, corresponding to human Gly-560 and/or Val-816, were constructed by site-directed mutagenesis and expressed in cells of a human embryonic kidney cell line (293T). In the transfected cells, KitR (Gly-559 + Val-814) and KitR (Val-814) were strikingly phosphorylated on tyrosine and activated in the absence of SCF, whereas tyrosine phosphorylation and activation of KitR (Gly-559) or wild-type KitR was modest or little, respectively. These results suggest that constitutive activation of KitR in HMC-1 results from the activating mutations of c-kit gene, and raise the possibility that the activating mutations, particularly at codon 814 of murine c-kit or at codon 816 of human c-kit, may participate in oncogenesis of mast cells.
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PMID:Activating mutations of the c-kit proto-oncogene in a human mast cell leukemia cell line. 751 80

Autonomous, factor-independent growth and differentiation of malignant cells in preleukemic and leukemic disease states is a well-recognized phenomenon and is often associated with a poor prognosis. Mast cells are distinct hematopoietic cells and express a unique profile of antigens. Growth and differentiation of normal mast cells is dependent on mast cell growth factor (MGF), the ligand of the c-kit protooncogene product. In this study, we screened for mast cell-lineage involvement in 52 patients suffering from myeloid leukemias, myelodysplastic syndromes (MDS), systemic mastocytosis, or other diseases by probing for mast cell-related molecules (c-kit, tryptase, histamine, and MGF) and by analyzing kit ligand/MGF-independent growth of mast cells in long-term suspension culture. Of the 52 patients tested, 2 patients with refractory anemia with excess of blast cells in transformation and 1 patient suffering from chronic myeloid leukemia blast crisis (CML-BC) were diagnosed as mastocytic disease. These patients were characterized by complex chromosomal abnormalities, splenomegaly, high percentages of circulating metachromatic cells (5% to 25%), high levels of cellular tryptase (> 10 ng/10(5) peripheral blood mononuclear cells/mL) and a tryptase/histamine (ng:ng) ratio greater than 1. The metachromatic cells expressed the mast-cell-related surface antigen c-kit, but not basophil-related antigens (CD11b, CDw17). Furthermore, in these 3 patients, spontaneous, MGF-independent growth of mast cells along with spontaneous synthesis of tryptase was demonstrable in long-term culture. No autocrine production, paracrine production, or overproduction of MGF was found. The spontaneous growth of mast cells could neither be abbrogated by addition of monoclonal antibodies (MoAbs) to c-kit nor by MoAbs against MGF (< 5% inhibition), whereas factor (MGF)-dependent differentiation of mast cells in these patients could be abbrogated by MoAbs to c-kit or MoAbs to MGF (> 70% inhibition, P < .001). In addition, serum MGF levels in these patients were within the normal range and MGF could not be detected in cell-free culture supernatants. All 3 patients showed rapid progression of disease and had a survival time of less than 1 year. In conclusion, we describe a unique form of transformation in MDS and CML-BC characterized by mast cell lineage involvement and factor-independent differentiation of mast cells. This form of leukemic transformation has to be delineated from chronic myeloid leukemia with basophilia or basophil crisis, from primary mast cell leukemia, and from monocytic leukemias and myelodysplastic disorders associated with basophilia.
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PMID:Kit ligand/mast cell growth factor-independent differentiation of mast cells in myelodysplasia and chronic myeloid leukemic blast crisis. 752 72

The c-kit protooncogene encodes a receptor tyrosine kinase that mediates signals required for differentiation, proliferation and survival of mast cells. We have already shown the constitutive activation of c-kit receptor tyrosine kinase (KIT) in a human mast cell leukemia line (HMC-1) and a murine mastocytoma cell line (P-815). We here examined whether such constitutive activation of KIT occurred in the rat tumor mast cell line RBL-2H3 as well, which is frequently used as a tool for studying functions of mast cells. In RBL-2H3 cells, KIT was constitutively phosphorylated on tyrosine and activated in the absence of autocrine production of its ligand, stem cell factor (SCF). Sequencing analysis revealed that one of c-kit genes of RBL-2H3 cells had a point mutation, resulting in amino acid substitution of Tyr for Asp in codon 817. When rat wild-type c-kit cDNA and mutant-type c-kit cDNA encoding KITTyr817 were transfected into cells of a human embryonic kidney cell line (293T), only mutant form KITTyr817 was constitutively phosphorylated on tyrosine and activated in the absence of SCF. Since mutations at the same Asp codon constitutively activated KIT in all the human HMC-1, murine P-815, and rat RBL-2H3 cell lines, and since the incorporation of antisense oligonucleotides of c-kit messenger RNA significantly suppressed the proliferation of RBL-2H3 cells, the activating mutations in the Asp codon of the c-kit gene appeared to be involved in neoplastic growth of mast cells.
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PMID:Substitution of an aspartic acid results in constitutive activation of c-kit receptor tyrosine kinase in a rat tumor mast cell line RBL-2H3. 753 1


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