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 de novo megakaryocytic leukemia fulfilling the FAB criteria is still an uncommonly recognized variant of acute leukemia. Many studies have shown that the megakaryocytic leukemic events may occur at a pluripotent stem cell level and clinical observations reveal that the megakaryocytic leukemias are diverse entities. The immunophenotyping using monoclonal antibodies against platelet specific surface antigens and the ultrastructural detection of platelet peroxidase reaction do not provide sufficiently useful information to determine whether a megakaryocytic leukemia is chronic, acute, therapy-responsive or therapy-unresponsive. More sophisticated techniques are required to further characterize megakaryocytic leukemic cells. In this review, we emphasize that megakaryocytic leukemic cells can be categorized into two groups; one with the PF4 mRNA, and the other without it, and that the expression of PF4 mRNA in the blasts could be a useful marker for the identification of mature megakaryoblasts. It seems that the patients with blasts expressing PF4 mRNA will have a longer survival and a better response to chemotherapy than those without PF4. We further discuss the fact that the detection of mRNAs of the IL-6 receptor, PDGF A- and B-chains, and TGF beta 1 in megakaryocytic leukemic cells will be useful to clarify the mechanisms involved in the proliferation of megakaryocytic leukemic cells and fibroblasts in the bone marrow. Furthermore, we reviewed data showing that megakaryocytic erythroid, and mast cell lineages share the nuclear transcription factor known as GF-1 (NF-E1 or Erf-1). We suggest that characterization of megakaryocytic leukemia should be performed using monoclonal antibodies against erythroid, megakaryocytic and mast cell lineages.
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PMID:Megakaryocytic leukemia and platelet factor 4. 133 50

The chimeric bcr-abl gene formed by the Philadelphia translocation is thought to initiate chronic myeloid leukemia. Engraftment of mice with bone marrow cells infected with a bcr-abl retrovirus has been shown to elicit multiple hematopoietic disorders, including a clonal but nontransplantable hyperproliferation of erythroid and/or mast cells. Culture of spleen and bone marrow cells from such mice usually yielded mast cell lines, even when erythroid disease dominated the primary animal. The mast cells, which carried the same proviral insert as the primary disease, generally grew slowly and were neither transplantable nor clonogenic in agar until they had been cultured for several months. Unexpectedly, several bcr-abl-induced lines switched in vitro from mast cell to megakaryocytic and/or erythroid character, and one became myeloid. The dramatic phenotypic shifts seem likely to involve changes occurring within progenitor cells maintaining the clone, rather than mutation of mature mast cells. The variant lines exhibited substantial spontaneous differentiation, despite being readily transplantable and therefore fully transformed. The production of hematopoietic growth factors by the mast cell lines and their phenotypic variants may implicate an autocrine loop in their evolution. These novel bcr-abl cell lines should aid in the study of genetic events in the progression from chronic to acute leukemia and facilitate analysis of hematopoietic lineage commitment.
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PMID:bcr-abl-Induced cell lines can switch from mast cell to erythroid or myeloid differentiation in vitro. 153 51

Six patients exhibiting severe pancytopenia or overt leukemia associated with myelofibrosis after chemotherapy for malignant disease have been investigated by immunologic techniques and ultrastructural cytochemistry. Initially, five patients displayed severe thrombocytopenia contrasting with mild neutropenia and anemia. Bone marrow biopsies showed a clear megakaryocytic proliferation and an excess of immature mononuclear cells. The demonstration of peroxidase activities at the ultrastructural level and immunofluorescence labeling with a panel of monoclonal antibodies, including an antiplatelet glycoprotein Ib and an antiglycoprotein IIb-IIIa complex, on blood or marrow cells, permitted identification of otherwise unidentifiable promegakaryoblastic proliferation. In two patients, the use of an immunoperoxidase technique with an antifactor VIII-R-Ag antibody has allowed direct confirmation of this diagnosis on bone marrow sections. This megakaryoblastic proliferation was not pure and was variably associated with blasts of other cell lines (erythroblasts or myeloblasts). Changes in the population of blasts were observed during evolution in two patients. The sixth patient had a mild thrombocytopenia associated with severe neutropenia and anemia. Bone marrow biopsy displayed a myelofibrosis and immature cells, without megakaryocytic proliferation. Ultrastructural study revealed a pure basophil-mast cell proliferation. In conclusion, in five of six patients with secondary acute leukemia associated with myelofibrosis, a proliferation of promegakaryoblasts was demonstrated using both immunofluorescent and ultrastructural cytochemical techniques.
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PMID:Therapy-related leukemia associated with myelofibrosis. Blast cell characterization in six cases. 638 Jul 2

A 12-year-old, female 5q- syndrome case of refractory anemia with excess of blasts in transformation (RAEB-T) evolving to mast cell leukemia is described. This case was admitted because of general fatigue, when her peripheral blood count revealed anemia and leukocytosis with basophil-like cells. RAEB-T was diagnosed based on the laboratory findings of her peripheral blood and bone marrow aspiration, which revealed over 10% peripheral blast cells and dysmyelopoietic changes in all three lineages. Chromosomal analysis of the bone marrow cells showed 46, XX, 5q-. Six months later, the RAEB-T phase evolved to acute leukemia, despite prednisolone, vitamin D3, oxymetholone and low-dose cytosine arabinoside treatment. She had remarkable pancytopenia, hemorrhage, and hepatosplenomegaly, which were not responsive to daunomycin, enocitabine, etoposide, and 6-mercaptopurine, and eventually died. This case was unique in that her karyotype changed to normal; 46, XX, and her blast cells were mast cell lineage during the overt leukemic phase. Interestingly, some blasts were intermediate cells possessing the ultrastructural features typical of both basophils and mast cells.
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PMID:[Mast cell leukemia evolved from RAEB-T (5q-syndrome) in a 12 year-old girl]. 869 90

Mastocytosis is a term collectively used for a heterogeneous group of disorders characterized by abnormal growth and accumulation of mast cells. Clinical symptoms occur from the release of chemical mediators and the pathologic infiltration of cells. Three major groups of patients with mastocytosis can be distinguished: i) cutaneous mastocytosis, ii) mastocytosis involving the skin and one or more extracutaneous organ(s), and iii) visceral mastocytosis without involvement of the skin. Groups ii) and iii) account for approximately 15-20% of all cases and have been referred to as systemic mastocytosis. Cutaneous mastocytosis typically presents as urticaria pigmentosa or diffuse cutaneous mastocytosis. These patients usually have a benign course. In contrast, systemic mastocytosis is a diffuse hematologic process with an increased risk to develop aggressive disease. In these patients, additional hematologic abnormalities or a second hematologic process, such as a myeloproliferative or myelodysplastic syndrome, or acute leukemia, may develop. Malignant mastocytosis and mast cell leukemia are rare forms of mastocytosis and characterized by uncontrolled and progressive proliferation and infiltration of mast cells in diverse organs. These patients often present without cutaneous lesions and have a very unfavorable prognosis. Because of the immature morphology of the cells it is often difficult to establish the diagnosis in such patients. However, the use of antibodies to mast cell antigens has recently improved the diagnostic efficiency in patients with suspected mast cell disease. No effective therapy for patients with malignant mastocytosis is known, although some patients may benefit from corticosteroid and interferon alpha treatment. The present article gives an overview of current knowledge about the biology, heterogeneity and treatment of human mastocytosis.
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PMID:Biology, classification and treatment of human mastocytosis. 876 23

Rearrangement of the tal-1 gene is the most frequent clonal marker in childhood T cell acute leukemia. Previously, tal-1 mRNA expression has been observed only in cells of the erythroid, mast cell, and megakaryocytic lineages and in blastic lymphoid cells of normal bone marrow, not in normal lymphocytes or monocytes of the peripheral blood (PB). In this study we addressed the question of tal-1 expression during normal hematopoietic development by performing reverse transcription-polymerase chain reaction (RT-PCR) on RNA from PB cells of 12 healthy donors. Ten of 10 unsorted samples were RT-PCR positive for tal-1 expression. Sorted T cells and monocytes from three donors showed tal-1 RT-PCR products. This is the first direct experimental evidence of tal-1 transcripts in these two normal PB cell types.
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PMID:Transcription of tal-1, a putative oncogene playing an important role in childhood T-ALL, can be shown in normal peripheral blood cells by a highly sensitive RT-PCR assay. 921 39

The association of mast cell diseases and some hematologic malignancies, usually myeloproliferative disorders, myelodysplastic syndromes, and acute leukemia is well recognized. We report the case of a patient with telangiectasia macularis eruptiva perstans, a rare form of cutaneous mastocytosis, and multiple myeloma, an association that has been described only twice in the literature. Parallel improvement of both conditions was observed under chemotherapy regimens for multiple myeloma. Pathogenesis remains unclear, although the abnormalities in the c-kit pathway may play a role in the proliferation of cells from both lineages.
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PMID:Telangiectasia macularis eruptiva perstans and multiple myeloma. 1104 37

An increase in mast cell (MC) numbers in hemopoietic tissues may be associated with (a) primary neoplastic MC disease (mastocytosis); (b) non-mast cell lineage myelogenous disorders (myelodysplastic or myeloproliferative syndromes and myeloid leukemias); or (c) reactive, i.e. non-clonal states (MC hyperplasia and reactive mastocytosis). However, the histologic discrimination between hyperplastic states and neoplastic MC proliferative disorders is sometimes very difficult. MC hyperplasia is characterized by a diffuse increase in mature, round or spindle-shaped, metachromatic MC that are loosely scattered throughout the tissue and do not form dense focal infiltrates, even in states of marked hyperplasia. However, loosely scattered MC are also a prominent feature of many cases of myelodysplastic syndromes and acute leukemia involving the MC lineage. In contrast, the demonstration of dense, focal and/or diffuse MC infiltrates can be regarded as indicative of primary MC disease/mastocytosis. In addition to the highly diagnostic focal MC infiltrates, mastocytosis may also present with a predominantly diffuse or a mixed (diffuse and focal) infiltration pattern. The relatively rare diffuse pattern is usually dominated by atypical, often hypogranulated or even non-metachromatic MC and is associated with the aggressive or frankly malignant subtypes of systemic mastocytosis and MC leukemia. Although the demonstration of MC infiltrates in Giemsa-stained tissue sections is still very important for the diagnosis of mastocytosis, immunohistochemical techniques using antibodies against MC-associated antigens such as tryptase or c-kit (CD117) are essential for the identification of highly atypical, hypogranulated MC, especially in MC leukemia, and for the detection of small and even minute MC infiltrates.
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PMID:Diagnosis of mastocytosis: general histopathological aspects, morphological criteria, and immunohistochemical findings. 1137 79

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

Transient leukemia of Down syndrome (DS-TL), also known as transient myeloproliferative disorder of Down syndrome (DS) and transient abnormal myelopoiesis of DS, occurs in approximately 10% of DS neonates and in phenotypically normal neonates with trisomy 21 mosaicism. In DS-TL, peripheral blood analysis shows variable numbers of blasts and, usually, thrombocytopenia; other cytopenias are uncommon. Bone marrow characteristics of DS-TL are, likewise, variable, though (in contrast to other leukemias) the bone marrow blast differential can be lower than the peripheral blood blast differential. The blasts of DS-TL typically show light microscopic, ultrastructural, and flow cytometric evidence of megakaryocyte differentiation. DS-TL neonates have a approximately 15% risk of developing potentially fatal liver disease and show <10% incidence of hydrops fetalis. Additional manifestations of DS-TL include cutaneous involvement, hyperviscosity, myelofibrosis, cardiopulmonary failure, splenomegaly, and spleen necrosis. Despite its typical transient nature, 20% to 30% of DS-TL patients develop overt (nontransient) acute leukemia, usually within 3 years and typically of the M7 phenotype (acute megakaryoblastic leukemia). The pathogenesis of DS-TL (and of subsequent acute leukemia) involves mutation of GATA1 (on chromosome X), which normally encodes a transcription factor integral to normal development of erythroid, megakaryocytic, and basophilic/mast cell lines. The pathogenetic role of trisomy 21 in DS-TL is unclear. Though indications for chemotherapy in DS-TL have not been firmly established, the blasts of DS-TL are sensitive to low-dose cytosine arabinoside.
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PMID:Transient leukemia (transient myeloproliferative disorder, transient abnormal myelopoiesis) of Down syndrome. 1699 19


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