Mastocytosis: A heterogenous group of disorders characterized by the abnormal increase of MAST CELLS in only the skin (MASTOCYTOSIS, CUTANEOUS), in extracutaneous tissues involving multiple organs (MASTOCYTOSIS, SYSTEMIC), or in solid tumors (MASTOCYTOMA).Mastocytosis, Systemic: A group of disorders caused by the abnormal proliferation of MAST CELLS in a variety of extracutaneous tissues including bone marrow, liver, spleen, lymph nodes, and gastrointestinal tract. Systemic mastocytosis is commonly seen in adults. These diseases are categorized on the basis of clinical features, pathologic findings, and prognosis.Mastocytosis, Cutaneous: Skin lesions due to abnormal infiltration of MAST CELLS. Cutaneous mastocytosis is confined to the skin without the involvement of other tissues or organs, and is mostly found in children. The three major variants are: URTICARIA PIGMENTOSA; diffuse cutaneous mastocytosis; and SOLITARY MASTOCYTOMA OF SKIN.Urticaria Pigmentosa: The most common form of cutaneous mastocytosis (MASTOCYTOSIS, CUTANEOUS) that occurs primarily in children. It is characterized by the multiple small reddish-brown pigmented pruritic macules and papules.Tryptases: A family of neutral serine proteases with TRYPSIN-like activity. Tryptases are primarily found in the SECRETORY GRANULES of MAST CELLS and are released during mast cell degranulation.Proto-Oncogene Proteins c-kit: A protein-tyrosine kinase receptor that is specific for STEM CELL FACTOR. This interaction is crucial for the development of hematopoietic, gonadal, and pigment stem cells. Genetic mutations that disrupt the expression of PROTO-ONCOGENE PROTEINS C-KIT are associated with PIEBALDISM, while overexpression or constitutive activation of the c-kit protein-tyrosine kinase is associated with tumorigenesis.Mast Cells: Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the BASOPHILS, mast cells contain large amounts of HISTAMINE and HEPARIN. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the STEM CELL FACTOR.Leukemia, Mast-Cell: A form of systemic mastocytosis (MASTOCYTOSIS, SYSTEMIC) characterized by the presence of large numbers of tissue MAST CELLS in the peripheral blood without skin lesions. It is a high-grade LEUKEMIA disease with bone marrow smear of >20% MAST CELLS, multi-organ failure and a short survival.Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.Methylhistamines: Histamine substituted in any position with one or more methyl groups. Many of these are agonists for the H1, H2, or both histamine receptors.Chymases: A family of neutral serine proteases with CHYMOTRYPSIN-like activity. Chymases are primarily found in the SECRETORY GRANULES of MAST CELLS and are released during mast cell degranulation.Bone Marrow Examination: Removal of bone marrow and evaluation of its histologic picture.Trichinella spiralis: A parasite of carnivorous mammals that causes TRICHINELLOSIS. It is especially common in rats and in swine fed uncooked garbage. Human infection is initiated by the consumption of raw or insufficiently cooked pork or other meat containing the encysted larvae.Anaphylaxis: An acute hypersensitivity reaction due to exposure to a previously encountered ANTIGEN. The reaction may include rapidly progressing URTICARIA, respiratory distress, vascular collapse, systemic SHOCK, and death.Mastocytoma: A solid tumor consisting of a dense infiltration of MAST CELLS. It is generally benign.Trichinellosis: An infection with TRICHINELLA. It is caused by eating raw or undercooked meat that is infected with larvae of nematode worms TRICHINELLA genus. All members of the TRICHINELLA genus can infect human in addition to TRICHINELLA SPIRALIS, the traditional etiological agent. It is distributed throughout much of the world and is re-emerging in some parts as a public health hazard and a food safety problem.Interleukin-9: A multifunctional cytokine secreted by primarily by activated TH2 CELLS that may play a role as a regulator of allergic INFLAMMATION. It has been shown to enhance the growth and CELL DIFFERENTIATION of MAST CELLS, and can act on a variety of other immune cells.Intestinal Diseases, Parasitic: Infections of the INTESTINES with PARASITES, commonly involving PARASITIC WORMS. Infections with roundworms (NEMATODE INFECTIONS) and tapeworms (CESTODE INFECTIONS) are also known as HELMINTHIASIS.Hydroxyzine: A histamine H1 receptor antagonist that is effective in the treatment of chronic urticaria, dermatitis, and histamine-mediated pruritus. Unlike its major metabolite CETIRIZINE, it does cause drowsiness. It is also effective as an antiemetic, for relief of anxiety and tension, and as a sedative.Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects.Trematode Infections: Infections caused by infestation with worms of the class Trematoda.Trematoda: Class of parasitic flukes consisting of three subclasses, Monogenea, Aspidogastrea, and Digenea. The digenetic trematodes are the only ones found in man. They are endoparasites and require two hosts to complete their life cycle.Stem Cell Factor: A hematopoietic growth factor and the ligand of the cell surface c-kit protein (PROTO-ONCOGENE PROTEINS C-KIT). It is expressed during embryogenesis and is a growth factor for a number of cell types including the MAST CELLS and the MELANOCYTES in addition to the HEMATOPOIETIC STEM CELLS.Eosinophilia: Abnormal increase of EOSINOPHILS in the blood, tissues or organs.Interleukin-5 Receptor alpha Subunit: A low affinity interleukin-5 receptor subunit that combines with the CYTOKINE RECEPTOR COMMON BETA SUBUNIT to form a high affinity receptor for INTERLEUKIN-5. Several isoforms of the interleukin-5 receptor alpha subunit exist due to multiple ALTERNATIVE SPLICING.Arthropod Venoms: Venoms from animals of the phylum Arthropoda. Those most investigated are from scorpions and spiders of the class Arachnidae and from ant, bee, and wasp families of the Insecta order Hymenoptera. The venoms contain protein toxins, enzymes, and other bioactive substances and may be lethal to man.Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body.Vulvar Diseases: Pathological processes of the VULVA.
Brentuximab Vedotin in Treating Patients With Advanced Systemic Mastocytosis or Mast Cell Leukemia... systemic mastocytosis or mast cell leukemia. Monoclonal antibod ... A diagnosis of systemic mastocytosis (SM) per 2008 World Health ... patients are no longer defined as systemic mastocytosis by the WHO). - Patients who have received any treatment with SGN-35 ... A Study of Brentuximab Vedotin (SGN-35) in CD30-Positive Systemic Mastocytosis With or Without an Associated Hematological ... A Study of Brentuximab Vedotin (SGN-35) in CD30-Positive Systemic Mastocytosis With or Without an Associated Hematological ...
Aberrant expression of CD30 in aggressive systemic mastocytosis and mast cell leukemia: a differential diagnosis to consider in...A most intriguing finding was that in contrast to normal MCs, neoplastic MCs in systemic mastocytosis (SM) aberrantly express ... Home » Medical Journals » Aberrant expression of CD30 in aggressive systemic mastocytosis and mast cell leukemia: a ... Aberrant expression of CD30 in aggressive systemic mastocytosis and mast cell leukemia: a differential diagnosis to consider in ... Aberrant expression of CD30 in aggressive systemic mastocytosis and mast cell leukemia: a differential diagnosis to consider in ...
Prognostically relevant breakdown of 123 patients with systemic mastocytosis associated with other myeloid malignancies. |...... systemic mastocytosis with chronic myelomonocytic leukemia, SM-MDS, and systemic mastocytosis with-acute leukemia, rather than ... Home » Medical Journals » Prognostically relevant breakdown of 123 patients with systemic mastocytosis associated with other ... The prognostic heterogeneity of the World Health Organization category of "systemic mastocytosis with associated clonal ... Prognostically relevant breakdown of 123 patients with systemic mastocytosis associated with other myeloid malignancies.. Head ...
TRYPT - Overview: Tryptase, SerumAssessing patients with systemic mastocytosis or mast cell activation syndrome ... Assessing patients with systemic mastocytosis or mast cell activation syndrome. Method Name A short description of the method ...
Systemic mastocytosis with associated clonal haematological non-mast cell lineage diseases: a histopathological challengeKeywords: mast cell, mastocytosis, systemic mastocytosis, systemic mastocytosis with associated clonal haematological non-mast ... The World Health Organisation (WHO) classification of mastocytosis includes four main categories of systemic mastocytosis (SM ... Valent P, Akin C, Sperr WR, et al. Diagnosis and treatment of systemic mastocytosis: state of the art. Br J Haematol 2003;122: ... Aims: Although systemic mastocytosis (SM) with an associated clonal haematological non-mast cell lineage disease (SM-AHNMD) is ...
Ivory vertebra and systemic mastocytosis. | MeAndMyMastcellsIvory vertebra and systemic mastocytosis.. Head for The Masto Townhall forum to debate this paper.. This article may be ... Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors.. Posted by admin in Medical Journals ... We report an unusual case of ivory vertebra sign that was due to systemic mastocytosis and improved with specific treatment. ... Although osteoporosis is the most common bone abnormality in systemic mastocytosis, an isolated sclerotic or lytic lesion may ...
Gene Expression Profile Of Systemic Mastocytosis Identified | MeAndMyMastcellsKIT D816V-associated systemic mastocytosis with eosinophilia and FIP1L1/PDGFRA-associated chronic eosinophilic leukemia are ... Gene Expression Profile Of Systemic Mastocytosis Identified. Below post translated from a Spanish article in diariomedico.com. ... of systemic mastocytosis, explained Andrés García Montero, one of the coordinators of this research group led by Salamanca's ... including systemic mastocytosis.. Posted by admin in Medical Journals ...
Allergen specific immunotherapy is safe and effective in patients with systemic mastocytosis and Hymenoptera allergy. |...Home » Medical Journals » Allergen specific immunotherapy is safe and effective in patients with systemic mastocytosis and ... A critical reappraisal of treatment response criteria in systemic mastocytosis and a proposal for revisions.. Posted by admin ... Allergen specific immunotherapy is safe and effective in patients with systemic mastocytosis and Hymenoptera allergy.. Head for ... Allergen specific immunotherapy is safe and effective in patients with systemic mastocytosis and Hymenoptera allergy. ...
Increased leukotriene E4 excretion in systemic mastocytosis. | MeAndMyMastcellsHome » Medical Journals » Increased leukotriene E4 excretion in systemic mastocytosis. Posted by admin on Jun 14, 2013 in ... Increased leukotriene E4 excretion in systemic mastocytosis.. Head for The Masto Townhall forum to debate this paper.. This ... LTE(4) levels have not been reported in systemic mastocytosis, a disorder with a large increase in mast cell numbers. Urinary ... The diagnosis of systemic mastocytosis was established using current World Health Organization criteria. Compared with a ...
Clinical Trials sub-cluster 24A 37-year-old female patient with systemic mastocytosis who was admitted with severe unexplained bleeding symptoms is studied. ... Abdominal portal-systemic collaterals may be protective from the formation and growth of oesophageal varices, but available ... BACKGROUND: Abdominal ultrasound can detect non-invasively the presence of abdominal portal-systemic collaterals in patients ... AIM: We aimed at investigating the relationship between abdominal portal-systemic collaterals and variceal formation ... ...
Proposal for a revised classification of systemic mastocytosis. | MeAndMyMastcellsHome » Medical Journals » Proposal for a revised classification of systemic mastocytosis. Posted by admin on Jun 14, 2013 in ... Eosinophilia in systemic mastocytosis: clinical and molecular correlates and prognostic significance.. Posted by admin in ... Systemic mastocytosis in adults: a review on prognosis and treatment based on 342 Mayo Clinic patients and current literature. ... Proposal for a revised classification of systemic mastocytosis.. Head for The Masto Townhall forum to debate this paper.. This ...
Isolated bone marrow mastocytosis: an underestimated subvariant of indolent systemic mastocytosis | Haematologica... systemic mastocytosis was grouped into 4 major clinical variants: 1) indolent systemic mastocytosis; 2) systemic mastocytosis ... 51 indolent systemic mastocytosis with skin involvement and 2 smoldering systemic mastocytosis patients are summarized in Table ... indolent systemic mastocytosis can be subclassified as smoldering systemic mastocytosis (SSM).2 ... a subvariant of indolent systemic mastocytosis recognized by the 2008 WHO classification.2 Diagnosis of systemic mastocytosis ...
Search of: 'Systemic mastocytosis' - List Results - ClinicalTrials.govIMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more... ...
BRIEF-Ab Science: CHMP adoptes negative opinion for masitinib in indolent systemic mastocytosis | ReutersREG-AB SCIENCE ANNOUNCES THAT CHMP HAS ADOPTED A NEGATIVE OPINION FOR MASITINIB IN INDOLENT SYSTEMIC MASTOCYTOSIS, PRIMARILY ... BRIEF-Ab Science: CHMP adoptes negative opinion for masitinib in indolent systemic mastocytosis. ... BRIEF-Ab Science: CHMP adoptes negative opinion for masitinib in indolent systemic mastocytosis ...
Phase II Study of Dasatinib in Philadelphia Chromosome-Negative Acute and Chronic Myeloid Diseases, Including Systemic...Mutation analysis of C-KIT in patients with myelodysplastic syndromes without mastocytosis and cases of systemic mastocytosis. ... Systemic mastocytosis. The overall response rate to dasatinib in patients with SM was 33% (11 of 33 patients treated). Two ... Treatment of adult systemic mastocytosis with interferon-α: results of a multicentre phase II trial on 20 patients. Br J ... Diagnosis and treatment of systemic mastocytosis: state of the art. Br J Haematol 2003;122:695-717. ...
Mastocytosis (cutaneous and systemic): Evaluation and diagnosis in childrenThese diseases can be limited to the skin (cutaneous mastocytosis [CM]) or involve extracutaneous tissues (systemic ... Mastocytosis describes a group of disorders in which there is pathologic accumulation of mast cells in tissues. ... See 'Mastocytosis (cutaneous and systemic): Evaluation and diagnosis in adults'.). ●(See 'Mastocytosis (cutaneous and systemic ... Mastocytosis (cutaneous and systemic): Epidemiology, pathogenesis, and clinical manifestations. *Mastocytosis (cutaneous and ...
Wiley Online Library: Search Results PageUrticaria and Mastocytosis. Rook's Textbook of Dermatology, Seventh Edition. C. E. H. Grattan, A. Kobza Black, Pages: 2313-2350 ... Comparative study of systemic psoralen and ultraviolet A and narrowband ultraviolet B in treatment of chronic urticaria. ...
Articles by Sameer Bakhshi, M.D. : Journal of Pediatric Hematology/OncologySystemic Mastocytosis Associated With Childhood Acute Myeloid Leukemia. Gogia, Ajay; Sharawat, Surender Kumar; Kumar, Rajive; ...
Oropharynx | Nicklaus Children's HospitalMastocytosis, diffuse cutaneous * Mastoiditis - redness and swelling behind ear * Mastoiditis - side view of head ... Systemic lupus erythematosus rash on the face * Teach children to brush * Teenage depression ...
The Cancer Letter Publications... three types of advanced systemic mastocytosis ...
Anaphylaxis: opportunities of stratified medicine for diagnosis and risk assessment - Wölbing - 2013 - Allergy - Wiley Online...1). If all those factors were known, the risk to develop systemic type I reactions and the grade of the reactions would be ... Anaphylaxis in patients with mastocytosis: a study on history, clinical features and risk factors in 120 patients. Allergy 2008 ... Predictors of severe systemic anaphylactic reactions in patients with Hymenoptera venom allergy: importance of baseline serum ... It is well accepted that the clinical manifestations of systemic type I allergic reactions depend on a complex process ...
Dermatology Articles (Diagnosis, Dermatologic Surgery, Histology, Prognosis, Follow-up) - Medscape ReferenceBullous Systemic Lupus Erythematosus (BSLE). *CREST Syndrome. *Dermatologic Manifestations of Eosinophilia-Myalgia Syndrome ... Mastocytosis. *Melanocytic Nevi. *Milia. *Multinucleate Cell Angiohistiocytoma. *Nevi of Ota and Ito ...
Camila Janniger MDDetection of antibasement zone antibodies in bullous systemic lupus erythematosus. J Am Acad Dermatol 1991; 24: 643-647. ... Childhood mastocytosis. Cutis 1992; 50: 187-189. *Janniger CK: Majocchi's granuloma. Cutis 1992; 50: 267-268. ... Dermatologic and systemic manifestations of syphilis. Am Fam Phys 1994; 50: 1013-1020. ... Dermatologic signs of selected systemic diseases. J Med 1999; 30: 3-12. ...
Cromoglicic acid - DrugBankCromoglicate is used as an ophthalmic solution to treat conjunctivitis and is taken orally to treat systemic mastocytosis and ...
Xanthelasmoidal mastocytosis: Xanthelasmoidal mastocytosis is a cutaneous condition characterized by numerous, confluent, yellow–tan papules.Diffuse cutaneous mastocytosis: Diffuse cutaneous mastocytosis has diffuse involvement in which the entire integument may be thickened and infiltrated with mast cells to produce a peculiar orange color, giving rise to the term "homme orange."James, William; Berger, Timothy; Elston, Dirk (2005).Urticaria pigmentosaTryptase: Tryptase (, ) is the most abundant secretory granule-derived serine proteinase contained in mast cells and has been used as a marker for mast cell activation. The biological function of tryptase is unclear.MotesanibDegranulationMast cell leukemiaBone marrow suppression: Bone marrow suppression or myelotoxicity (adjective myelotoxic) or myelosuppression is the decrease in production of cells responsible for providing immunity (leukocytes), carrying oxygen (erythrocytes), and/or those responsible for normal blood clotting (thrombocytes). Bone marrow suppression is a serious side effect of chemotherapy and certain drugs affecting the immune system such as azathioprine.Bone marrow examination: Bone marrow examination refers to the pathologic analysis of samples of bone marrow obtained by bone marrow biopsy (often called a trephine biopsy) and bone marrow aspiration. Bone marrow examination is used in the diagnosis of a number of conditions, including leukemia, multiple myeloma, lymphoma, anemia, and pancytopenia.Anaphylaxis Campaign: The Anaphylaxis Campaign is the only UK charity to exclusively meet the needs of the growing numbers of people at risk from severe allergic reactions by providing information and support relating to foods and other triggers such as latex, drugs and insect stings.The Anaphylaxis CampaignInternational Conference on Trichinellosis: The International Commission on Trichinellosis (ICT) was created in 1958 in Budapest and is aiming to exchange information on the biology, the physiopathology, the epidemiology, the immunology, and the clinical aspects of trichinellosis in humans and animals. Prevention is a primary goal (see ICTweb pages).Intestinal parasiteHydroxyzineBithynia fuchsiana: Bithynia fuchsiana is a species of small freshwater snail with a gill and an operculum, an aquatic gastropod mollusk in the family Bithyniidae.Philophthalmus gralliAncestimEosinophilic gastroenteritisScolopendra: Scolopendra (through Latin from Greek "skolopendra") is a genus of centipedes of the family Scolopendridae.Brain biopsyLabial fusion
(1/111) CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate therapy.
Imatinib mesylate is effective in the treatment of hematologic malignancies that are characterized by either abl- or PDGFR beta- activating mutations. The drug is also active in a subset of patients with eosinophilic disorders and systemic mast cell disease (SMCD). Recently, a novel tyrosine kinase that is generated from fusion of the Fip1-like 1 (FIP1L1) and PDGFR alpha (PDGFRA) genes has been identified as a therapeutic target for imatinib mesylate in hypereosinophilic syndrome (HES). We used fluorescence in situ hybridization (FISH) to detect deletion of the CHIC2 locus at 4q12 as a surrogate for the FIP1L1-PDGFRA fusion. CHIC2 deletion was observed in bone marrow cells for 3 of 5 patients with SMCD associated with eosinophilia. Deletion of this locus and expression of the FIP1L1-platelet-derived growth factor receptor alpha (PDGFRA) fusion was also documented in enriched eosinophils, neutrophils, or mononuclear cells by both FISH and reverse transcriptase-polymerase chain reaction (RT-PCR) for one patient. While all 3 patients with the FIP1L1-PDGFRA rearrangement achieved a sustained complete response with imatinib mesylate therapy, the other two, both carrying the c-kit Asp816 to Val (Asp816Val) mutation, did not. These observations suggest that the FIP1L1-PDGFRA rearrangement occurs in an early hematopoietic progenitor and suggests that the molecular pathogenesis for a subset of SMCD patients is similar to that of HES. Screening for the FIP1L1-PDGFRA rearrangement and Asp816Val mutation will advance rational therapy decisions in SMCD. (+info)
(2/111) Cladribine therapy for systemic mastocytosis.
Patients with systemic mastocytosis (SM) can suffer from disabling symptoms related to mast cell mediator release or mast cell infiltration, requiring mast cell eradication. In the present absence of any curative therapy, a recent case report describing the efficacy of cladribine showed promising results. In a pilot study, the efficacy of cladribine (0.10-0.13 mg/kg in a 2-hour infusion, days 1-5; repeated at 4-8 weeks until 6 cycles) was studied. Ten patients with SM with severe symptoms were treated. Four patients were classified as having indolent or smoldering mastocytosis, 3 as having aggressive systemic mastocytosis, and 3 as having SM with an accompanying hematologic malignancy. Nine patients received 6 courses, 1 patient stopped because of toxicodermia. All responded concerning signs, symptoms, and mast cell parameters (serum tryptase and urinary histamine metabolite excretion), although none achieved a complete remission. Prolonged follow-up is required, as response is ongoing in most cases. One patient relapsed within 11 months and showed a second response. Side effects were mainly related to bone marrow suppression. Single-agent cladribine is an effective and relatively safe treatment for severe systemic mastocytosis. The optimal dose and schedule need to be explored. (+info)
(3/111) Expression of Bcl-2 and Bcl-xL in cutaneous and bone marrow lesions of mastocytosis.
Mastocytosis is a rare disease characterized by accumulation of mast cells in tissues. To investigate whether an altered regulation of mast cell apoptosis might be involved in the pathogenesis of mastocytosis, expression of the apoptosis-preventing molecules bcl-2 and bcl-xL was studied by immunohistochemistry in skin and bone marrow lesions of mastocytosis patients. In addition, reverse transcription-polymerase chain reaction was used to investigate levels of bcl-2 and bcl-xL mRNA in cutaneous mastocytosis lesions. Since activating mutations of c-kit are known to be associated with some forms of mastocytosis, human mast cell cultures were also stimulated via c-kit and the expression of bcl-2 and bcl-xL was assessed by immunoblotting. In patients with mastocytosis, the expression of bcl-2 protein but not bcl-xL in cutaneous mast cells was significantly enhanced, compared to healthy controls. Evaluating different subgroups of adult and pediatric mastocytosis patients, all groups were found to express significantly increased levels of bcl-2 protein, and none of the patient groups was found to overexpress bcl-xL, with the exception of solitary mastocytomas that showed a tendency for up-regulated bcl-xL protein. Furthermore, the expression of bcl-2 mRNA was significantly enhanced in cutaneous lesions of adult and pediatric patients, while bcl-xL mRNA levels were only slightly increased in pediatric, but not in adult patients with mastocytosis. In contrast to the skin lesions, bone marrow infiltrates of patients with systemic mastocytosis showed only low or absent immunoreactivity for bcl-2, but marked expression of bcl-xL. In vitro, stimulation of two different mast cell culture systems by activation of c-kit resulted in up-regulation of bcl-2 and also in an increase of bcl-xL, although less pronounced. Thus, overexpression of bcl-2 and bcl-xL leading to prolonged survival of mast cells may contribute to the pathogenesis of mastocytosis. Our findings may help to develop new strategies for the treatment of this disease. (+info)
(4/111) 17-Allylamino-17-demethoxygeldanamycin (17-AAG) is effective in down-regulating mutated, constitutively activated KIT protein in human mast cells.
Mutations in the proto-oncogene c-kit cause constitutive kinase activity of its product, KIT protein, and are associated with human mastocytosis and gastrointestinal stromal tumors (GISTs). Although currently available tyrosine kinase inhibitors are effective in the treatment of GISTs, there has been limited success in the treatment of mastocytosis. 17-Allylamino-17-demethoxygeldanamycin (17-AAG), a benzoquinoid ansamycin antibiotic, which binds to heat shock protein 90 (hsp90) causes destabilization of various hsp90-dependent kinases important in oncogenesis. Treatment with 17-AAG of the mast cell line HMC-1.2, harboring the Asp816Val and Val560Gly KIT mutations, and the cell line HMC-1.1, harboring a single Val560Gly mutation, causes both the level and activity of KIT and downstream signaling molecules AKT and STAT3 to be down-regulated following drug exposure. These data were validated using Cos-7 cells transfected with wild-type and mutated KIT. 17-AAG promotes cell death of both HMC mast cell lines. In addition, neoplastic mast cells isolated from patients with mastocytosis, incubated with 17-AAG ex vivo, are selectively sensitive to the drug compared to the mononuclear fraction. These data provide compelling evidence that 17-AAG may be effective in the treatment of c-kit-related diseases including mastocytosis, GISTs, mast cell leukemia, subtypes of acute myelogenous leukemia, and testicular cancer. (+info)
(5/111) Bone marrow biopsies for the diagnosis of systemic mastocytosis: is one biopsy sufficient?
The medical records of 21 patients evaluated for mastocytosis and 2 patients seen for follow-up of known mastocytosis who underwent bilateral iliac crest aspirations and biopsies were reviewed retrospectively to determine whether mastocytosis could be confirmed in each of a patient's biopsy specimens. In 19 cases (83%), each biopsy specimen showed evidence of mastocytosis; however in 4 cases (17%), only 1 of 2 biopsy sites revealed mastocytosis. Compared with the 4 patients with only a unilateral positive biopsy result, the bilateral group had significantly higher urinary excretion of 11beta-prostaglandin F2alpha, higher serum tryptase levels, and higher serum calcitonin values, and a higher percentage had splenomegaly (37% [7/19] vs 0% [0/4]). The 2 groups could not be distinguished by the main initial symptom(s), presence of urticaria pigmentosa, or other laboratory findings (alkaline phosphatase, aspartate transaminase, or hemoglobin concentrations or total WBC, total eosinophil, or platelet counts). Bilateral biopsies might be useful for diagnosing early systemic mastocytosis or detecting minimal bone marrow involvement. (+info)
(6/111) A novel form of mastocytosis associated with a transmembrane c-kit mutation and response to imatinib.
Mutational analysis of the c-kit gene in a patient with a previously undescribed variant of mast cell disease revealed a germline mutation, Phe522Cys, within the transmembrane portion of the Kit receptor protein. Transfection experiments revealed that the mutation caused ligand-independent autophosphorylation of Kit, which was inhibited by the tyrosine kinase inhibitor imatinib mesylate. The patient's bone marrow biopsy and aspirate displayed unique pathologic features with the presence of excessive numbers of mature-appearing mast cells and absence of aberrant mast cell surface expression of CD2, CD25, and CD35. Therapy with imatinib mesylate resulted in a dramatic improvement in mast cell burden and clinical symptoms. These results highlight the significance of the transmembrane region of Kit in activation of the molecule and its importance in mast cell development and suggest a role for screening for transmembrane c-kit mutations in patients with mastocytosis in association with the decision to use imatinib mesylate. (+info)
(7/111) Systemic mastocytosis with associated clonal haematological non-mast cell lineage diseases: a histopathological challenge.
AIMS: Although systemic mastocytosis (SM) with an associated clonal haematological non-mast cell lineage disease (SM-AHNMD) is a major subtype of SM, little is known about its frequency among myelogenous neoplasms, and mastocytosis in particular, or about AHNMD subtype frequencies. METHODS: Approximately 19500 routine bone marrow biopsies were evaluated. Immunostaining with antibodies against tryptase, KIT, and CD25 and molecular analysis for detection of C-KIT point mutations were performed in approximately 550/4100 myelogenous malignancies including mastocytosis, almost all subtypes of myelodysplastic syndrome (MDS), myelodysplastic/myeloproliferative syndrome (MDS/MPD), MPD, and acute myeloid leukaemia (AML). RESULTS: SM was rare-it was diagnosed in only 64 bone marrows (0.3%) and made up 1.5% of myelogenous tumours. SM-AHNMD was the second most frequent subtype (20). SM-AHNMD was never included in the clinical differential diagnoses and was confirmed histologically in most cases only after appropriate immunostaining. The abnormal mast cell phenotype was confirmed by immunohistochemical demonstration of tryptase and CD25 coexpression. The following associated haematological neoplasms were found: MDS/MPS, AML, MPS, MDS, plasma cell myeloma, and unclassifiable myelogenous malignancy. C-KIT point mutations were detected in 16 of 20 cases. CONCLUSIONS: SM-AHNMD can be diagnosed histologically in bone marrow trephines only after immunostaining with antibodies against tryptase, KIT, and CD25. Eighteen of 20 AHNMDs were of myeloid origin. C-KIT point mutations were present in 16 of 20 cases. The prognostic relevance of detecting SM associated with another haematological neoplasm remains unclear, but mast cell resistance to most cytoreductive agents is of major importance for treatment planning. (+info)
(8/111) FIP1L1-PDGFRA and c-kit D816V mutation-based clonality studies in systemic mast cell disease associated with eosinophilia.
Laboratory methods to detect both FIP1L1-PDGFRA and c-kit D816V mutations were combined with immunomagnetic cell separation to study the extent of clonal involvement by both myeloid and lymphoid cells in 3 patients with systemic mastocytosis associated with eosinophilia. The results suggested an early stem cell origin for the FIP1L1-PDGFRA mutation. (+info)
- On the basis of clinical and pathologic follow-up, 10 of 30 (33%) patients were diagnosed with SM and 20 of 30 (67%) with limited cutaneous mastocytosis ( CM ). Although cutaneous mast cell density was slightly higher in patients with SM compared to those with limited CM (P=0.047), neither mast cell cytomorphology nor infiltration pattern correlated with underlying systemic disease. (meandmymastcells.com)
- 1 Pure cutaneous mastocytosis and mast cell sarcoma are listed as separate, non-systemic entities. (pubmedcentralcanada.ca)
- See 'Treatment and prognosis of cutaneous mastocytosis' . (uptodate.com)
- Sixty-one patients showed classic skin lesions: a diagnosis of indolent systemic mastocytosis (ISMs+) was made in 51 of 61 subjects, 2 patients were diagnosed with smoldering systemic mastocytosis and 8 were classified as cutaneous mastocytosis. (haematologica.org)
- Although systemic mastocytosis (SM) with an associated clonal haematological non-mast cell lineage disease (SM-AHNMD) is a major subtype of SM, little is known about its frequency among myelogenous neoplasms, and mastocytosis in particular, or about AHNMD subtype frequencies. (pubmedcentralcanada.ca)
- Aberrant expression of CD30 in aggressive systemic mastocytosis and mast cell leukemia: a differential diagnosis to consider in aggressive hematopoietic CD30-positive neoplasms. (meandmymastcells.com)
- A lack of skin lesions has been described in cases of aggressive systemic mastocytosis and mast cell leukemia, but also in bone marrow mastocytosis (BMM), a subvariant of indolent systemic mastocytosis recognized by the 2008 WHO classification. (haematologica.org)
- CD25 expression on cutaneous mast cells from adult patients presenting with urticaria pigmentosa is predictive of systemic mastocytosis. (meandmymastcells.com)
- Home » Medical Journals » Ivory vertebra and systemic mastocytosis. (meandmymastcells.com)
- Home » Medical Journals » Increased leukotriene E4 excretion in systemic mastocytosis. (meandmymastcells.com)
- On the basis of the presence of two or more B-findings, indolent systemic mastocytosis can be subclassified as smoldering systemic mastocytosis (SSM). (haematologica.org)
- Moreover, indolent systemic mastocytosis without skin lesions has been frequently reported in patients with systemic allergic reaction to hymenoptera venom and raised basal tryptase. (haematologica.org)
- We report the characteristics of 99 consecutive indolent systemic mastocytosis patients, diagnosed or revised according to the 2008 WHO classification 2 from January 2005 to December 2009 at the Multidisciplinary Outpatient Clinic for Mastocytosis in Verona, Italy. (haematologica.org)
- Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. (meandmymastcells.com)
- Mast cells from different molecular and prognostic subtypes of systemic mastocytosis display distinct immunophenotypes. (meandmymastcells.com)
- Immunostaining with antibodies against tryptase, KIT, and CD25 and molecular analysis for detection of C-KIT point mutations were performed in approximately 550/4100 myelogenous malignancies including mastocytosis, almost all subtypes of myelodysplastic syndrome (MDS), myelodysplastic/myeloproliferative syndrome (MDS/MPD), MPD, and acute myeloid leukaemia (AML). (pubmedcentralcanada.ca)
- Because a diagnosis of SM can be made when the major criterion and at least one of the minor criteria are fulfilled, the haematopathologist plays a crucial role in diagnosing or excluding mastocytosis in a given tissue specimen. (pubmedcentralcanada.ca)
- How frequent is mastocytosis within the spectrum of haematological diseases on the basis of an evaluation of routinely processed bone marrow trephine specimens and how often is SM-AHNMD included in the clinical differential diagnosis? (pubmedcentralcanada.ca)
- See 'Mastocytosis (cutaneous and systemic): Evaluation and diagnosis in adults' . (uptodate.com)
- 1 Diagnosis of systemic mastocytosis can also be made in the presence of at least 3 minor criteria. (haematologica.org)
- 2 Diagnosis of systemic mastocytosis in the absence of typical skin involvement presents a challenge for clinicians. (haematologica.org)
- Mast cells and mastocytosis. (meandmymastcells.com)
- 2 Recently, immunohistochemistry on routinely processed bone marrow biopsy specimens demonstrated that CD25 is expressed exclusively on mast cells of those cases with morphologically and molecular biologically confirmed mastocytosis, but not on mast cells in states of mast cell hyperplasia, enabling an abnormal or neoplastic phenotype of mast cells to be defined. (pubmedcentralcanada.ca)
- Mastocytosis describes a group of disorders in which there is pathologic accumulation of mast cells in tissues. (uptodate.com)
- Systemic mastocytosis (SM) is a heterogeneous disorder characterized by the proliferation and accumulation of atypical mast cells (MC) in tissues, principally in the bone marrow (BM) and skin. (haematologica.org)
- Phase II study of dasatinib in Philadelphia chromosome-negative acute and chronic myeloid diseases, including systemic mastocytosis. (meandmymastcells.com)
- Prognostically relevant breakdown of 123 patients with systemic mastocytosis associated with other myeloid malignancies. (meandmymastcells.com)
- See 'Mastocytosis (cutaneous and systemic): Epidemiology, pathogenesis, and clinical manifestations' . (uptodate.com)
- Mastocytosis: a disease of the hematopoietic stem cell. (meandmymastcells.com)
- Urinary LTE(4) from patients referred for symptoms potentially due to mast cell degranulation or systemic mastocytosis was measured by a commercial cysteinyl leukotriene enzyme immunoassay kit. (meandmymastcells.com)
- We report an unusual case of ivory vertebra sign that was due to systemic mastocytosis and improved with specific treatment. (meandmymastcells.com)
- The ivory vertebra sign should not be considered idiopathic until tests are done for mastocytosis, particularly given the availability of effective treatments. (meandmymastcells.com)