Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Systemic mastocytosis (SM) is a myeloproliferative disease affecting multipotent and/or mast cell-committed hematopoietic progenitor cells. In a significant subgroup of patients (10-35%), an associated clonal hematologic non-mast cell lineage disorder (AHNMD) occurs. These AHNMDs can be classified according to recently established WHO criteria. Most AHNMDs resemble myeloid malignancies such as acute myeloid leukemia, myeloproliferative disorders or myelodysplastic syndromes. In only a few cases, lymphoproliferative disorders are diagnosed. Patients with SM-AHNMD have a less favorable prognosis concerning survival when compared to indolent SM. No general guidelines for the treatment of patients with SM-AHNMD have been established so far. A reasonable straightforward approach may be to treat the AHNMD in those patients in the same way as if no coexisting SM exists.
 ...
PMID:Spectrum of associated clonal hematologic non-mast cell lineage disorders occurring in patients with systemic mastocytosis. 1191 25

An association between mastocytosis and monoclonal gammopathy is a relatively rare but well recognized clinical finding. In the majority of cases, however, overt myeloma or lymphoma is not detectable morphologically. Here we describe the case of a 51 year-old male patient first presenting with paresis of the right facial nerve and the serological finding of IgM kappa paraproteinemia. The patient did not have organomegaly, lytic bone lesions, or urticaria pigmentosa-type skin lesions. Histological examination of a trephine biopsy specimen revealed the unusual coexistence of plasma cell myeloma and mastocytosis. Immunohistochemically, plasma cells were found to exhibit a monotypic staining for Ig heavy chain mu and Ig light chain kappa, thus confirming their neoplastic nature. Mast cells showed prominent spindling and formed dense multifocal infiltrates, thus enabling the diagnosis of bone marrow mastocytosis. Immunohistochemically, mast cells expressed tryptase, chymase, and KIT (CD117). In addition, aberrant expression of CD25 on mast cells was detected, confirming the coexistence of a neoplastic mast cell-proliferative disorder. According to the WHO proposal for classification of hematopoietic malignancies, this unique case, showing the association of two very rare haematologic neoplasms, can therefore best be referred to as bone marrow mastocytosis associated with IgM kappa plasma cell myeloma (SM-AHNMD).
 ...
PMID:Bone marrow mastocytosis associated with IgM kappa plasma cell myeloma. 1516 Sep 59

In mast cell (MC) disorders (mastocytosis), clinical symptoms are caused by the release of chemical mediators from MCs, the pathologic infiltration of neoplastic MCs in tissues, or both. Cutaneous mastocytosis is a benign disease in which MC infiltration is confined to the skin. In pediatric cases cutaneous mastocytosis might regress spontaneously. Systemic mastocytosis (SM) is more frequently diagnosed in adults and is a persistent (clonal) disease of bone marrow-derived myelomastocytic progenitors. The somatic c-kit mutation D816V is found in the majority of such patients. The natural clinical course in SM is variable. Whereas most patients remain at the indolent stage for many years, some have aggressive SM (ASM) at diagnosis. Other patients have an associated clonal hematologic non-MC lineage disease (AHNMD). MC leukemia (MCL) is a rare disease variant characterized by circulating MCs and fatal disease progression. The diagnoses of ASM, SM-AHNMD, and MCL might be confused with a variety of endocrinologic, vascular, or immunologic disorders. It is therefore of particular importance to be aware of the possibility of an underlying (malignant) MC disease in patients with unexplained vascular instability, unexplained (anaphylactoid) shock, idiopathic flushing, diarrhea, headache, and other symptoms that might be mediator related. An important diagnostic clue in such cases is an increased serum tryptase level. The current review provides an overview of mastocytosis and its subvariants and a practical guide that might help to delineate mastocytosis from unrelated systemic disorders.
 ...
PMID:Diagnosis and classification of mast cell proliferative disorders: delineation from immunologic diseases and non-mast cell hematopoietic neoplasms. 1524 37

Based on generally accepted criteria and the WHO-classification, a subset of patients with systemic mastocytosis (SM) have (or develop) an associated clonal hematologic non-mast cell lineage disease (SM-AHNMD). We describe a case of SM with coexisting chronic eosinophilic leukemia (SM-CEL). The patient, a 51-year-old male, was first seen in 1992 with small-sized infiltrates of spindle-shaped mast cells in his marrow, and marked eosinophilia. Retrospectively, a CHIC2 deletion and the FIP1L1/PDGFRalpha fusion gene-product were demonstrable by FISH analysis and RT-PCR, respectively. SM-associated organopathy or mediator-related symptoms were not recorded. However, the patient developed cardiomyopathy. Therapy with interferon-alpha, hydroxyurea, and corticosteroids were without effects. By contrast, therapy with imatinib was followed by a fast and sustained response with complete and stable regression of eosinophilia, drop in eosinophil cationic protein, and decrease of serum tryptase to normal levels. This case provides further evidence for the potential of co-existence of SM with a primary eosinophilic disorder (CEL) defined by the FIP1L1/PDGFRalpha fusion gene. Because of the availability of a superior targeted drug (imatinib), it is of importance to screen for FIP1L1/PDGFRalpha in suspected CEL with or without co-existing SM.
 ...
PMID:Systemic mastocytosis (SM) associated with chronic eosinophilic leukemia (SM-CEL): detection of FIP1L1/PDGFRalpha, classification by WHO criteria, and response to therapy with imatinib. 1640 18

Systemic mast cell disorders in most instances appear to be clonal disorders of the mast cell and its progenitor. Symptoms result from a pathological release of mast cell mediators and a destructive mast cell infiltration. Cutaneous mastocytosis is most frequently seen in children and may regress. Systemic mastocytosis (SM) is a persistent disease. A somatic c-kit mutation at codon 816 is often detectable in haematopoietic cells. The clinical course of mastocytosis is variable, ranging from indolent to aggressive. Five categories of disease are recognized: Indolent SM, aggressive SM, SM with associated clonal haematological non-mast cell-lineage disease (AHNMD) and mast cell leukaemia (MCL). In SM-AHNMD, additional genetic abnormalities have been reported. Patients with cutaneous or indolent systemic disease are treated symptomatically. Patients with aggressive disease are candidates for cytoreductive therapy. The use of 'Kit-targeting' tyrosine kinase inhibitors are best selected following a mutational analysis of c-kit. For instance, the D816V mutation appears to be associated with relative resistance against imatinib. However, imatinib has been used with success in patients with SM-hypereosinophilic syndrome (HES) and the FIPL1/PDGFRA fusion gene and in a patient with mastocytosis with a mutation outside of codon 816. The value of bone marrow transplantation remains under investigation.
 ...
PMID:Mastocytosis. 1660 39

Mastocytosis is a neoplastic disease involving mast cells (MC) and their CD34+ progenitors. Symptoms in mastocytosis are caused by biological mediators released from MC and/or the infiltration of neoplastic MC in various organs, the skin and the bone marrow being predominantly involved. A WHO consensus classification for mastocytosis exists, which is widely accepted and includes three major categories: (1) Cutaneous mastocytosis (CM), a benign disease in which MC infiltration is confined to the skin, is preferentially seen in young children and exhibits a marked tendency to regress spontaneously. (2) Systemic mastocytosis (SM) which is commonly diagnosed in adults and includes four major subtypes: (i) indolent SM (ISM, the most common form involving mainly skin and bone marrow); (ii) a unique subcategory termed SM with an associated non-mast cell clonal hematological disease (SM-AHNMD); (iii) aggressive SM usually presenting without skin lesions, and (iv) MC leukemia, probably representing the rarest variant of human leukemias. (3) The extremely rare localized extracutaneous MC neoplasms, either presenting as malignancy (MC sarcoma) or as benign tumor termed extracutaneous mastocytoma. Diagnostic criteria for mastocytosis are available and are widely accepted. SM criteria include one major criterion (multifocal compact tissue infiltration by MC) and four minor criteria: (1) prominent spindling of MC; (2) atypical immunophenotype of MC with coexpression of CD2 and/or CD25 (antigens which have not been found to be expressed on normal/reactive MC); (3) activating (somatic) point mutations of the c-kit proto-oncogene usually involving exon 17, with the imatinib-resistant type D816V being most frequent, and (4) persistently elevated serum tryptase level (>20 ng/ml). To establish the diagnosis of SM, at least one major and one minor criterion, or at least three minor criteria, have to be fulfilled. The natural clinical course of mastocytosis is variable. Most patients, in particular those with CM and ISM, remain in an indolent stage over many years or even decades, while others, in particular those with aggressive SM, SM-AHNMD, or mast cell leukemia, show a progressive course, usually with a fatal outcome.
 ...
PMID:Mastocytosis: state of the art. 1758 83

Clinical phenotype in systemic mastocytosis (SM) is markedly variable, which complicates prognostication and decision making regarding the choice and timing of therapy. In a retrospective study of 342 consecutive adult patients with SM seen at the Mayo Clinic between 1976 and 2007, disease subdesignation according to the World Health Organization (WHO) proposal was indolent (ISM) in 159 (46%), with associated clonal hematologic non-mast cell lineage disease (SM-AHNMD) in 138 (40%), aggressive (ASM) in 41 (12%), and mast cell leukemia in 4 (1%). KITD816V was detected in bone marrow-derived DNA by allele-specific polymerase chain reaction (PCR) in 68% of 165 patients evaluated (ISM, 78%; ASM, 82%; SM-AHNMD, 60%; P = .03); JAK2V617F was detected in 4%, all in SM-AHNMD. Compared with those with nonindolent SM, life expectancy in ISM was superior and not significantly different from that of the age- and sex-matched US population. In addition, multivariable analysis identified advanced age, weight loss, anemia, thrombocytopenia, hypoalbuminemia, and excess bone marrow blasts as independent adverse prognostic factors for survival. The current study validates the prognostic relevance of the WHO subclassification of SM and provides additional information of value in terms of both risk stratification and interpretation of clinical presentation and laboratory results.
 ...
PMID:Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. 1936 19

In a substantial number of patients with systemic mastocytosis (SM), an associated clonal haematological non-mast cell lineage disease (AHNMD) is detectable. Although most of these patients display KIT mutations, especially KIT(D816V), little is known about their exact frequency and their distribution in AHNMD subtypes. We examined 48 patients with SM-AHNMD for the presence of mutant KIT in the SM and AHNMD components of the disease. Mast cells and AHNMD cells were obtained from immunostained bone marrow sections by laser microdissection and examined by melting point analysis of nested-PCR products. KIT(D816V) was found in AHNMD cells in the vast majority of patients with SM-chronic myelomonocytic leukaemia (CMML, 89%). Unexpectedly, KIT(D816V) was far less frequently detectable in AHNMD cells in patients with SM-myeloproliferative neoplasm (MPN, 20%) and SM-acute myeloid leukaemia (AML, 30%). None of the patients with lymphoproliferative AHNMDs displayed KIT codon 816 mutations in AHNMD cells (0/8). In FIP1L1/PDGFRA-positive chronic eosinophilic leukaemia (CEL), neither the SM nor the CEL component of the disease exhibited the KIT mutation. Our findings demonstrate that KIT codon 816 mutations are variably present in AHNMD cells in patients with SM-AHNMD, depending on the subtype of AHNMD. The high frequency of KIT(D816V) in neoplastic mast cells and leukaemic myelomonocytic cells in SM-CMML may point to a common precursor in these patients, and may have implications for the biology of the disease and the development of KIT-targeting therapies.
 ...
PMID:Variable presence of KITD816V in clonal haematological non-mast cell lineage diseases associated with systemic mastocytosis (SM-AHNMD). 2011 69

Systemic mastocytosis with associated clonal haematological non-mast cell lineage disease (SM-AHNMD) is a heterogeneous group of mast cell disorders with different clinical, pathologic and underlying molecular characteristics. While myelomonocytic/myeloid neoplasia overwhelmingly predominates the AHNMD component, lymphoproliferative disorders rarely occur as an AHNMD component of SM-AHNMD. Here we report two cases of SM-AHNMD, in which the AHNMD component is chronic lymphocytic leukemia in one case, and concurrent chronic lymphocytic leukemia as well as plasma cell myeloma in another case. To the best of our knowledge, this is the first case report of SM-AHNMD with chronic lymphocytic leukemia and plasma cell dyscrasia simultaneously.
 ...
PMID:Systemic mastocytosis in association with chronic lymphocytic leukemia and plasma cell myeloma. 2049 Mar 36

An elderly woman presented with anaemia, thrombocytopenia and multifocal lytic and sclerotic bone lesions. Trephine bone marrow biopsy demonstrated widespread involvement by systemic mastocytosis (SM). The neoplastic mast cells expressed mast cell tryptase, CD117, CD25 and CD9, and were accompanied by compact sheets of atypical large histiocytic cells, expressing CD68, CD4, S-100 protein and CD14, in keeping with a concomitant histiocytosis (SM-AHNMD). Mutation analysis revealed the activating point mutation D816V of the c-kit proto-oncogene in microdissected pooled bone marrow mast cells. Partial remission was achieved using interferon alpha. To the best of our knowledge this is the first reported case of SM-AHNMD with histiocytosis as the non-mast cell component.
 ...
PMID:Systemic mastocytosis (SM) and associated malignant bone marrow histiocytosis - a hitherto undescribed form of SM-AHNMD. 2186 66


1 2 Next >>