Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Mast cell disease. 149 Jun 22

A myelodysplastic syndrome (MDS), type 5 (RAEB-t), and systemic mastocytosis affecting the spleen, the splenic lymph nodes, the bone marrow and the liver were diagnosed in a 38-year-old woman. The clinical course was complicated by splenic vein thromboses and iliac artery embolism. The thrombotic episodes might be secondary to mast cell mediator release. A complete remission of the MDS was obtained by allogeneic bone marrow transplantation, but the mastocytosis persisted. Thus, the possibility that the mast cell originates from a common myeloid precursor cell may be questioned.
 ...
PMID:Persistence of systemic mastocytosis after allogeneic bone marrow transplantation in spite of complete remission of the associated myelodysplastic syndrome. 176 77

A 64-year-old man had urticaria pigmentosa and myelodysplasia (refractory anemia with excess blast cells; partial trisomy 8 syndrome) without increased numbers of marrow mast cells. Clonal marrow assays in agar demonstrated normal to increased colony-forming units of granulocytes/macrophages. In long-term liquid cultures containing mast cell growth factor (interleukin 3), his marrow cells proliferated after 3 weeks to produce abnormal myeloid precursors similar to those in the corresponding marrow aspirate specimen. Cells with basophilic-staining granules were less abundant in comparison with normal marrow specimens cultured similarly. These results suggest that the mast cells in this patient are not of the same clone as the preleukemic marrow cells, although the possible marrow-cell origin of urticaria pigmentosa mast cells cannot be excluded. Previous reports suggest that urticaria pigmentosa without systemic mastocytosis occurs as a nonspecific abnormality in a variety of myeloid, lymphoid, and nonhematologic malignancies. Our data also support this hypothesis that urticaria pigmentosa is a reactive process rather than a manifestation of clonal proliferation of the primary malignancy.
 ...
PMID:Urticaria pigmentosa and preleukemia: evidence for reactive mast cell proliferation. 205 Aug 59

Blood findings in 61 cases of generalized mastocytosis (GM) were evaluated. The cases were divided into two major variants: Systemic mastocytosis (SM; n = 34) with urticaria pigmentosa-like skin lesions, and malignant mastocytosis (MM; n = 27), without skin involvement. The following results were obtained: (1) Significant differences between MM and SM were found in the main haematological parameters (erythrocyte, platelet and leucocyte counts and haemoglobin level); normal values were found in 16 of the SM cases, but never in MM. (2) The main pathological findings were: in SM, anaemia (9/34) and leucocytosis (5/34); and in MM, leucocytosis (19/27), monocytosis (14/27), eosinophilia (12/27), bicytopenia (12/27, mostly anaemia with thrombocytopenia), basophilia (10/27) and isolated anaemia (7/27). (3) The major finding was a significant difference between MM and SM in the incidence of myeloproliferative disorders (MPD), myelodysplasia and mast cell leukaemia (MCL): these disorders occurred in 23 (92%) MM patients, but only in two (6%) SM patients (P less than 0.001). The four instances of MCL and two of myelodysplasia all occurred with MM. Of the 19 cases of MPD, six (SM, 1; MM, 5) were acute variants (acute myeloid and myelomonocytic leukaemias) and 13 (SM, 1; MM, 12) were chronic variants. No case of malignant lymphoma was noted. (4) The blood picture in 10 of 13 chronic MPD cases represented an atypical chronic myeloid leukaemia for which the preliminary descriptive term 'mastocytosis-associated MPD' is proposed. (5) A survey of 103 published cases (SM, 77; MM, 26) yielded similar findings, including a high incidence of MPD and MCL in MM. These findings add further weight to the argument for recognizing SM and MM as two separate entities.
 ...
PMID:Blood findings in generalized mastocytosis: evidence of frequent simultaneous occurrence of myeloproliferative disorders. 201 71

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.
 ...
PMID:Kit ligand/mast cell growth factor-independent differentiation of mast cells in myelodysplasia and chronic myeloid leukemic blast crisis. 752 72

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.
 ...
PMID:Biology, classification and treatment of human mastocytosis. 876 23

The stem cell factor (SCF)c-kit receptor interaction plays a critical role in the development and survival of mast cells. Several studies have also associated c-kit receptor mutations with the human diseases, mastocytosis and piebaldism. Overexpression of c-kit has been reported to be associated with myeloproliferative disorders and myelodysplastic syndromes. Using peripheral blood mononuclear cells (PBMCs) from 11 patients with indolent mastocytosis (category I), mastocytosis with an associated hematologic disorder (category II), or aggressive mastocytosis (category III); a patient with CMML unassociated with mastocytosis, and PBMCs from 13 normal subjects, we examined the level of expression of c-kit mRNA along with other c-kit isoforms to determine if overexpression of the c-kit receptor was associated with mastocytosis. Using quantitative competitive PCR, c-kit mRNA levels on average were found to be statistically elevated in the five patients with mastocytosis with an associated hematologic disorder and in the patient with aggressive mastocytosis as compared with controls, but not elevated in patients with indolent mastocytosis. The relative mRNA expression for the two c-kit isoforms was not significantly different in the mastocytosis patients compared with controls. This demonstration of the overexpression of c-kit mRNA in mastocytosis, and particularly those patients with clinical evidence of myelodysplastic syndrome, adds evidence to support the conclusion that mastocytosis, at least in some patients, is a feature of myelodysplasia; and suggests that determination of c-kit mRNA expression in PBMCs may provide an additional approach to assessing prognosis.
 ...
PMID:Elevated expression of the proto-oncogene c-kit in patients with mastocytosis. 951 79

Myelodysplastic syndromes (MDS) may be accompanied by systemic mastocytosis. The mechanisms which play a role in the evolution of mastocytosis, however, are not well understood. We report on a case of refractory and anemia with ringed sideroblasts (RARS), and co-existing bone marrow mastocytosis. Compact mast cell (MC) infiltrates were detected in bone marrow sections by immunohistochemistry using an antibody to tryptase. In addition, the MC were found to express c-kit, the tyrosine kinase receptor for MGF (mast cell growth factor = stem cell factor, SCF). Activating point mutations in the kinase domain of c-kit (often found in mastocytosis) were not detectable. However, the mononuclear cells (MNC) of the bone marrow expressed mRNA specific for MITF, a transcription factor that regulates expression of c-kit and differentiation of MC. Surprisingly, the c-kit ligand SCF was found to augment expression of MITF mRNA in bone marrow MNC. Whether this augmentation represents a general response (preventing loss of growth factor receptor expression during cell maturation) common to all types of hemopoietic progenitors, or is confined to (some forms of) mastocytosis, remains unknown.
 ...
PMID:Detection of mi transcription factor (MITF) mRNA in a case of myelodysplastic syndrome and bone marrow mastocytosis. 955 2

Mastocytosis is a term used for a spectrum of disorders characterized by abnormal growth and accumulation of mast cells. The cutaneous variants of the disease have to be distinguished from systemic mastocytosis (SM), in which at least one extracutaneous organ is involved. In contrast to cutaneous mastocytosis, SM is often associated with another hematologic neoplasm. In most cases clonal myeloid malignancies such as a myeloproliferative or myelodysplastic syndrome occur. In a few cases of SM, however, clonal lymphoid disorders have been described. We here report on a case of SM associated with multiple myeloma. At first presentation, the 48-year old female patient showed monoclonal IgGlambda gammopathy and bone marrow (BM) mastocytosis, but no BM plasma cell infiltrates. Eight years later, the patient presented with BM mastocytosis and overt multiple myeloma. The co-existence of myeloma and mastocytosis was demonstrable by staining serial BM sections with antibodies against mast cell tryptase, CD68R, and the plasma cell marker VS38c. Interphase FISH analysis of BM sections revealed a numeric gain of chromosome 5 and chromosome 7 in the plasma cells but not in the mast cell infiltrates, thereby confirming the presence of two different neoplastic cell populations. To our knowledge, this is the first report describing the co-existence of multiple myeloma and mastocytosis.
 ...
PMID:A case of bone marrow mastocytosis associated with multiple myeloma. 961 35

The quantitative measurement of the expression of both cytoplasmic and surface CD63 antigen by human mast cells from both normal and pathological bone marrow samples was studied by use of flow cytometry. Our major goal was to analyze whether in vivo CD63 expression by human bone marrow mast cells could be useful to discriminate bone marrow mast cells from patients with mastocytosis from other conditions. For that purpose, a total of 65 subjects corresponding to 12 healthy volunteers, 25 B-cell chronic lymphoproliferative disorders, 5 reactive bone marrow samples, 4 myelodysplastic syndromes, and 19 mastocytosis were analyzed. The expression of both surface and cytoplasmic CD63 by human bone marrow mast cells is clearly demonstrated. Our results show that high amounts of CD63 are present in human bone marrow mast cells most of it corresponding to an intracellular localization. No significant differences in CD63 expression were observed as regards both total and cytoplasmic CD63, except for higher CD63 levels in adult patients with mastocytosis (P = 0.05). By contrast, the mean level of surface CD63 significantly varied between the different groups of individuals. Accordingly, patients with monoclonal gammopathies displayed a slight decrease (P = 0.1) in surface CD63 expression, whereas bone marrow mast cells from adults with indolent systemic mast cell disease showed significantly (P = 0.0005) higher levels of surface CD63 as compared to healthy controls.
 ...
PMID:Human bone marrow mast cells from indolent systemic mast cell disease constitutively express increased amounts of the CD63 protein on their surface. 982 8


1 2 3 4 5 6 7 Next >>