Disease relevance of Mastocytosis, Systemic

• FIP1L1-PDGFRA is a relatively infrequent but treatment-relevant mutation in primary eosinophilia that is indicative of an underlying systemic mastocytosis [1].
• These results show that mastocytosis is a disorder of a pluripotential hematopoietic progenitor cell that gives rise to B cells and monocytes in addition to mast cells and that the affected clone shows variable expansion in these lineages in the peripheral blood of patients with systemic mastocytosis [2].
• Constitutively activated forms of the transmembrane receptor tyrosine kinase c-KIT have been associated with systemic mast cell disease, acute myeloid leukemia, and gastrointestinal stromal tumors [3].
• However, KIT activation loop mutations involving codon D816 that are typically found in AML, systemic mastocytosis, and seminoma are insensitive to imatinib mesylate (IC50 > 5-10 micromol/L), and acquired KIT activation loop mutations can be associated with imatinib mesylate resistance in GIST [4].
• Diarrhea and malabsorption were due to mast cell infiltration of the bowel rather than to histamine. patients with signs of systemic mastocytosis should have careful evaluations and be followed up to prevent development of malabsorption and tetany [5].

High impact information on Mastocytosis, Systemic

• Treatment of systemic mast-cell disease with cladribine [6].
• In 17 patients with systemic mastocytosis, concentrations of tryptase in plasma were linearly related to those of histamine (P less than 0.01) [7].
• Nonatopic control subjects with systemic mastocytosis had normal functional and phenotypic data, suggesting that chronic activation of atopic T cells in vivo by circulating histamine does not explain the abnormal histamine-induced suppressor response [8].
• Secretory diarrhea and prostaglandin D2 overproduction in systemic mastocytosis [9].
• Oral disodium cromoglycate in the treatment of systemic mastocytosis [10].

Chemical compound and disease context of Mastocytosis, Systemic

• Treatment of adult systemic mastocytosis with a PAF-acether antagonist BN52063 [11].
• Effect of cimetidine on gastric hypersecretion and diarrhea in systemic mastocytosis [12].
• Heparin activity in systemic mastocytosis [13].
• Mithramycin in the treatment of systemic mastocytosis [14].
• The majority of patients with systemic mast cell disease express the imatinib-resistant Asp816Val (D816V) mutation in the KIT receptor tyrosine kinase [15].

Biological context of Mastocytosis, Systemic

• We report on a patient with systemic mastocytosis with an activating point mutation of the c-kit gene [16].
• The effect of pamidronate on lumbar spine bone density and pain in osteoporosis secondary to systemic mastocytosis [17].
• In order to investigate the possible involvement of airway mast cells in bronchial hyperresponsiveness (BHR), we examined whether a patient with systemic mastocytosis would demonstrate BHR against ultrasonically nebulized distilled water (UNDW) and histamine inhalation challenge [18].
• The patient consented to discontinue the H2-receptor antagonist, and to have the following values measured: serum and urine concentrations of cimetidine: complete blood count (CBC) with differential, serum chemistry, and urinalysis; and systemic mastocytosis symptomatology [19].

Anatomical context of Mastocytosis, Systemic

• Tryptase, a protease produced by all mast cells, was evaluated as a clinical marker of systemic mastocytosis [20].
• Two patients had systemic mastocytosis and histamine excess, marked gastric acid and pepsin hypersecretion, and diarrhea [12].
• In cell surface staining experiments, bone marrow (BM) MCs in systemic mastocytosis (n = 12) as well as HMC-1 cells (30%-80%) were found to express the T11-1 and T11-2 (but not T11-3) epitopes of CD2 [21].
• We report the in vitro and in vivo effects of granulocyte macrophage colony stimulating factor (GM-CSF), a known inhibitor of in vitro mast cell differentiation, in a patient with benign, adult-onset systemic mastocytosis [22].
• The measurement of these chemical mediators (histamine, tryptase and prostaglandin D2 and their metabolites) in body fluids is useful for the diagnosis and the laboratory evaluation of patients with systemic mastocytosis [23].

Gene context of Mastocytosis, Systemic

• CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate therapy [24].
• It is hypothesized that expression of CD2 is associated with pathologic accumulation and function of MCs in systemic mastocytosis [21].
• The alpha form of human tryptase is the predominant type present in blood at baseline in normal subjects and is elevated in those with systemic mastocytosis [20].
• Evidence for the involvement of a hematopoietic progenitor cell in systemic mastocytosis from single-cell analysis of mutations in the c-kit gene [2].
• Vesicular monoamine transporter 2 (VMAT2) expression in hematopoietic cells and in patients with systemic mastocytosis [25].

Analytical, diagnostic and therapeutic context of Mastocytosis, Systemic

• To test this hypothesis, intradermal titrations (0.02 ml of solution from 1 ng/ml to 2 micrograms/ml) of histamine and morphine sulfate (MS) (10 ng/ml to 10 micrograms/ml) were administered to normal volunteers (N = 15), patients with recurrent, unexplained anaphylaxis (N = 10), and patients with systemic mastocytosis (N = 18) [26].
• Utility of paraffin section immunohistochemistry for C-KIT (CD117) in the differential diagnosis of systemic mast cell disease involving the bone marrow [27].
• Serum tryptase and the laboratory diagnosis of systemic mastocytosis [28].
• In the present study, expression of target antigens on CD34+/CD38- cells was analysed by multi-color flow cytometry in patients with AML (n = 18), myelodysplastic syndromes (MDS, n = 6), chronic myeloid leukemia (CML, n = 8) and systemic mastocytosis (SM, n = 9) [29].
• METHODS: The DNA of microdissected bone marrow cells from a patient with systemic mastocytosis and associated CMML was analysed for the presence of the c-kit mutation Asp 816 to Val by means of HinfI digestion and direct sequencing of semi-nested polymerase chain reaction (PCR) products [30].

References