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)

The hematopoietic growth factor interleukin (IL)-3 is a potent regulator of blood cell proliferation. It promotes the survival, proliferation, and development of hematopoietic stem cells and committed progenitor cells of the granulocyte-macrophage, erythrocyte, eosinophil, basophil, megakaryocyte, mast cell, and lymphocyte lineages. In addition, IL-3 enhances mature myeloid cell functions such as phagocytosis and activation of basophils and eosinophils, as well as monocyte cytotoxicity. The first phase of clinical trials suggested that IL-3 may augment myelopoiesis in a number of clinical conditions. It may be efficacious for treatment of primary marrow disorders, including myelodysplastic syndromes and aplastic anemia. However, replacement therapy with IL-3 alone is probably not sufficient to obtain maximal stimulation of myelopoiesis. Preclinical and clinical studies published to date suggest that sequential use or combinations of growth factors will be needed to obtain optimal hematopoietic responses.
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PMID:Interleukin-3. Its biology and potential uses in pediatric hematology/oncology. 178 68

The relationship of bone marrow mast cell counts to prognosis was investigated in 48 patients with preleukaemic myelodysplasia, in 59 patients with aplastic anemia and in a DMBA induced myelodysplasia/leukaemia rat model. In patients with myelodysplasia terminating in overt leukaemia the number of mast cells per square millimeter was not correlated to duration of the preleukaemic course. Leukaemia development probabilities of patients at risk were not different for low and elevated mast cell counts. In aplastic anaemia, however, a lower bone marrow mast cell count was related to a higher survival probability and longer survival time. In the animal model no significant differences could be found between myelodysplastic, leukaemic, and control animals.
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PMID:Bone marrow mast cell reaction in preleukaemic myelodysplasia and in aplastic anaemia. 392 Aug 22

High bone marrow mast cell counts before and after marrow transplantation have been reported to predict graft rejection in aplastic anemia. We tested this association by studying marrow specimens from 73 consecutive patients allografted for severe aplastic anemia, 21 of whom rejected. Mast cell counts per unit area were performed on aspirate smears stained with Wright-Giemsa stain and on particle sections, clot sections, and biopsy specimens of marrow stained with toluidine blue. The ranges in both rejecting and nonrejecting patients with both methods were wide. Smear counts were more variable and correlated poorly with section counts (correlation coefficient: +0.003). We found no differences between rejecting and nonrejecting patients, either before or after grafting, with regard to mast cell counts in marrow. Also alterations in myeloid:erythroid ratios bore no detectable relationship to rejection.
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PMID:Marrow mast cell counts do not predict bone marrow graft rejection. 702

Although systemic mastocytosis (SM) is a well-defined hematologic neoplasm, it is sometimes difficult to discriminate between SM and a reactive mast cell (MC) hyperplasia. We describe a patient with aplastic anemia who was treated with recombinant stem cell factor (SCF). In response to SCF, the patient showed transient hematologic improvement and developed a marked increase in MC as well as a transient increase in serum tryptase. Histologic and immunohistochemical examination revealed a huge increase in MC in the bone marrow with focal infiltrates similar to SM. However, most of the SM-criteria were not met: First, MC showed normal cytomorphological characteristics without significant atypias (no cytoplasmic extensions, no oval nuclei, no hypogranulated cytoplasm). Furthermore, bone marrow MC were CD2- and CD25-negative and did not exhibit the C-KIT 2468 A-->T mutation (Asp-816-Val). After discontinuation of SCF the MC hyperplasia resolved confirming its reactive nature. Based on our case and similar cases mimicking mastocytosis, it seems of importance to apply recently established SM criteria in order to discriminate between reactive MC hyperplasia and true mastocytosis with certainty.
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PMID:Stem cell factor-induced bone marrow mast cell hyperplasia mimicking systemic mastocytosis (SM): histopathologic and morphologic evaluation with special reference to recently established SM-criteria. 1200 61

Recent reports of myelodysplastic syndrome/acute myeloid leukemia (t-MDS/AML) developing after treatment with immunosuppressants and granulocyte colony-stimulating factor (G-CSF) has raised the question of whether previously unrecognized myelodysplastic features had been present or whether actual transformation had occurred. We undertook a multi-institutional study of 112 children with aplastic anemia diagnosed between 1976 and 1996 and then treated with immunosuppressants with or without G-CSF. In each case, bone marrow specimens were tested at study entry and every 6 months for 3 years to detect t-MDS/AML as defined by morphologic and molecular/cytogenetic criteria. As of December 2001, all eligible patients had been followed for a median of 3 years. Morphologic abnormalities were found in 17 cases. The patients in 4 of these cases had clonal cytogenetic abnormalities and received MDS diagnoses. The morphologic features of the patients with and without clonal cytogenetic abnormalities were indistinguishable. However, the mast cell content was lower in cases with cytogenetic abnormalities than in cases without them. An elucidation of the role of mast cells may provide information about the differences between aplastic anemia and MDS or about the transition of aplastic anemia to MDS.
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PMID:Serial morphologic observation of bone marrow in aplastic anemia in children. 1615 20

The development of mature blood cells from hematopoietic stem cells is regulated by transcription factors that control and coordinate the expression of lineage-specific genes. The GATA family consists of six transcription factors that function in hematopoietic and endodermal development. Among them, GATA-1 is expressed in erythroid, megakaryocytic, eosinophil and mast cell lineages, and GATA-2 is expressed in stem and progenitor cells, at more immature stage compared with GATA-1. Based on the characteristic phenotypes of GATA-1 and GATA-2 mutant mice, it has been suggested that mutations of these GATA genes in humans may result in the onset of certain clinical diseases. To date, mutations of GATA-1 gene have been found in inherited anemia and thrombocytopenia, and Down syndrome-related acute leukemia, which exhibits megakaryocytic phenotypes and frequently occurs in patients with Down syndrome. In contrast, no mutation of GATA-2 gene has been identified in hematological diseases; however, we found the expression level of GATA-2 is significantly decreased in CD34 positive cells in patients with aplastic anemia. Since GATA-2 functions in the proliferation of hematopoietic stem cells, the reduction of GATA-2 expression in CD34 positive cells may result in the decreased number of hematopoietic stem cells, which is the characteristic feature of aplastic anemia. Based on these lines of evidence, some types of hematological diseases may be defined as transcription factor diseases.
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PMID:GATA transcription factors and hematological diseases. 1696 Mar 39

Reactive bone marrow mast cells reliably lack the morphologic, immunophenotypic, and molecular features of systemic mastocytosis (SM). We report two unusual cases of acquired aplastic anemia (AA) in which multifocal aggregates of bone marrow mast cells fulfilled morphologic and immunophenotypic criteria for SM according to the World Health Organization 2008 classification. In the absence of clinical symptoms attributable to SM, the patients were treated with immunosuppressive therapy directed towards AA. Clinical follow-up and subsequent bone marrow examination revealed no evidence of overt SM in either patient. These cases represent, to our knowledge, the first reported instances in which criteria for SM have been fulfilled in the presence of AA. However, given the clinical courses followed by our patients, the incidental identification of mast cell lesions consistent with indolent SM may be of uncertain significance in the setting of AA.
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PMID:Two cases of concomitant acquired aplastic anemia and systemic mastocytosis. 2418 60

The purpose of this section is to educate the reader on how to successfully manage patients with a hypersensitivity reaction to clopidogrel using desensitization protocol based on various published protocols. Additionally, we will define drug desensitization, and describe the possible mechanism of how desensitization may function as alternative medication. The indications/contraindications for desensitization will be reviewed. The different published clopidogrel desensitization protocols will be discussed. Based on those protocols, we recommend a protocol we feel is safe and efficacious. Clopidogrel is a thienopyridine antiplatelet drug widely used for treatment and also employed for secondary prevention regarding a range of cardiovascular diseases. However, it has been reported to cause hypersensitivity reactions. Ticlopidine is an alternative medication that can be considered when patients have an allergic reaction to clopidogrel. Additionally, ticlopidine is associated with increased risk causing potentially life-threatening adverse reactions to include: Aplastic anemia, reversible neutropenia, and thrombotic thrombocytopenia purpura vs. clopidogrel. Thus, clopidogrel desensitization offers an attractive alternative. Drug desensitization is defined as causing a temporary state of tolerance to a specific medication responsible for a hypersensitivity reaction. Furthermore, drug desensitization can only be maintained by continuous administration of this drug. Discussion: The exact immunologically mediated mechanism of how rapid oral desensitization works is not fully understood and yet to be defined. Ultimately desensitization results in causing antigen-specific mast cell tolerance. Various protocols have been published. The length of desensitization ranged from 2 h using 9 doses to 7 h using 15 doses. Recommendations: Taking the above into account, we recommend using a modification to the protocol that has the largest number of patients to undergo a standardized clopidogrel desensitization. This approach is shorter, as time has immense importance for these patients. Dosing starts at 10 mg dose and with 60 min intervals between doses, this now becomes a 4 h desensitization protocol.
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PMID:Clopidogrel Desensitization: Background and Recommendations for Use of a Rapid (4 Hour) Protocol. 3037 98