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Danish Medical Journal Mar 2012The mast cell lives a hidden life, but it is implicated in several physiological reactions. Its ability to react to different stimuli impacts a variety of conditions... (Review)
Review
INTRODUCTION
The mast cell lives a hidden life, but it is implicated in several physiological reactions. Its ability to react to different stimuli impacts a variety of conditions such as asthma, atopic dermatitis, urticaria and anaphylaxis. It is not until recent decades that the evolution of the cell has been described and its fascinating biology has only recently been depicted. We here give a review of systemic mastocytosis in regards to cell biology, diagnostic approaches and clinical practice.
METHODS
A search was made in PubMed in August 2011 entering the keywords: mastocytosis, (systemic, cutaneous, aggressive), mast cell leukaemia, mast cell sarcoma, chromosome, mutation, haematology and treatment.
RESULTS
Mastocytosis is characterized by an abnormal proliferation of mast cells, which accumulate in one or several organ systems, primarily the skin and bone marrow. The disease is clinically heterogeneous and varies from a relatively benign condition with isolated cutaneous lesions to a very aggressive systemic condition with a grave prognosis. The condition affects men and women equally. Children are especially affected by the cutaneous form. In most children, the condition will improve or remit spontaneously before adulthood. Mastocytosis in adults, however, is more often systemic and tends to persist.
CONCLUSION
Patients with mastocytosis represent a heterogeneous group in terms of clinical presentation, management and prognosis. Furthermore, a range of medical specialties serve as the primary entrance to health services, which can be a challenge in respect of achieving uniform management. In order to improve diagnostics and management of systemic mastocytosis, the European Competence Network on Mastocytosis has been established. Patients under suspicion of systemic mastocytosis should be conferred with or referred to a haematological and a dermatological/allergological department.
Topics: Glucocorticoids; Histamine Antagonists; Humans; Mast Cells; Mastocytosis, Systemic; Prognosis
PubMed: 22381091
DOI: No ID Found -
Haematologica Oct 2016Systemic mastocytosis is a heterogeneous disease characterized by the accumulation of neoplastic mast cells in the bone marrow and other organ organs/tissues. Mutations... (Review)
Review
Systemic mastocytosis is a heterogeneous disease characterized by the accumulation of neoplastic mast cells in the bone marrow and other organ organs/tissues. Mutations in KIT, most frequently KIT D816V, are detected in over 80% of all systemic mastocytosis patients. While most systemic mastocytosis patients suffer from an indolent disease variant, some present with more aggressive variants, collectively called "advanced systemic mastocytosis", which include aggressive systemic mastocytosis, systemic mastocytosis with an associated hematologic, clonal non mast cell-lineage disease, and mast cell leukemia. Whereas patients with indolent systemic mastocytosis have a near normal life expectancy, patients with advanced systemic mastocytosis have a reduced life expectancy. Although cladribine and interferon-alpha are of benefit in a group of patients with advanced systemic mastocytosis, no curative therapy is available for these patients except possible allogeneic hematopoietic stem cell transplantation. Recent studies have also revealed additional somatic defects (apart from mutations in KIT) in a majority of patients with advanced systemic mastocytosis. These include TET2, SRSF2, ASXL1, RUNX1, JAK2, and/or RAS mutations, which may adversely impact prognosis and survival in particular systemic mastocytosis with an associated hematological neoplasm. In addition, several additional signaling molecules involved in the abnormal proliferation of mast cells in systemic mastocytosis have been identified. These advances have led to a better understanding of the biology of advanced systemic mastocytosis and to the development of new targeted treatment concepts. Herein, we review the biology and pathogenesis of advanced systemic mastocytosis, with a special focus on novel molecular findings as well as current and evolving therapeutic options.
Topics: Hematologic Neoplasms; Humans; Mast Cells; Mastocytosis, Systemic; Molecular Targeted Therapy; Mutation
PubMed: 27694501
DOI: 10.3324/haematol.2016.146563 -
Blood Mar 2017Over the past few years, substantial advances have been made in understanding the pathogenesis, evolution, and complexity of mast cell neoplasms. New diagnostic and... (Review)
Review
Over the past few years, substantial advances have been made in understanding the pathogenesis, evolution, and complexity of mast cell neoplasms. New diagnostic and prognostic parameters and novel therapeutic targets with demonstrable clinical impact have been identified. Several of these new markers, molecular targets, and therapeutic approaches have been validated and translated into clinical practice. At the same time, the classification of mastocytosis and related diagnostic criteria have been refined and updated by the consensus group and the World Health Organization (WHO). As a result, more specific therapies tailored toward prognostic subgroups of patients have been developed. Emerging treatment concepts use drugs directed against KIT and other relevant targets in neoplastic mast cells and will hopefully receive recognition by health authorities in the near future. This article provides an overview of recent developments in the field, with emphasis on the updated WHO classification, refined criteria, additional prognostic parameters, and novel therapeutic approaches. Based on these emerging concepts, the prognosis, quality of life, and survival of patients with advanced mastocytosis are expected to improve in the coming years.
Topics: Humans; Mastocytosis; Molecular Targeted Therapy; Prognosis; Quality of Life; World Health Organization
PubMed: 28031180
DOI: 10.1182/blood-2016-09-731893 -
Haematologica Nov 2018Mastocytosis is a term used to denote a group of rare diseases characterized by an abnormal accumulation of neoplastic mast cells in various tissues and organs. In most... (Review)
Review
Mastocytosis is a term used to denote a group of rare diseases characterized by an abnormal accumulation of neoplastic mast cells in various tissues and organs. In most patients with systemic mastocytosis, the neoplastic cells carry activating mutations in Progress in mastocytosis research has long been hindered by the lack of suitable models, such as permanent human mast cell lines. In fact, only a few human mast cell lines are available to date: HMC-1, LAD1/2, LUVA, ROSA and MCPV-1. The HMC-1 and LAD1/2 cell lines were derived from patients with mast cell leukemia. By contrast, the more recently established LUVA, ROSA and MCPV-1 cell lines were derived from CD34 cells of non-mastocytosis donors. While some of these cell lines (LAD1/2, LUVA, ROSA and MCPV-1) do not harbor mutations, HMC-1 and ROSA cells exhibit activating mutations found in mastocytosis and have thus been used to study disease pathogenesis. In addition, these cell lines are increasingly employed to validate new therapeutic targets and to screen for effects of new targeted drugs. Recently, the ROSA subclone has been successfully used to generate a unique model of advanced mastocytosis by injection into immunocompromised mice. Such a model may allow validation of data obtained with targeted drugs directed against mastocytosis. In this review, we discuss the major characteristics of all available human mast cell lines, with particular emphasis on the use of HMC-1 and ROSA cells in preclinical therapeutic research in mastocytosis.
Topics: Animals; Cell Line, Tumor; Humans; Mast Cells; Mastocytosis, Systemic; Models, Biological
PubMed: 29976735
DOI: 10.3324/haematol.2018.195867 -
Acta Dermato-venereologica Mar 2016Mastocytosis comprises a heterogeneous group of disorders characterized by clonal, neoplastic proliferation of mast cells accumulating in one or multiple organs. In the... (Review)
Review
Mastocytosis comprises a heterogeneous group of disorders characterized by clonal, neoplastic proliferation of mast cells accumulating in one or multiple organs. In the majority of cases skin involvement is the first clinical manifestation of the disease. Clinical work-up consists of a combination of morphological, immunohistochemical, flow cytometric immunophenotyping and molecular examination. Cutaneous mastocytosis predominates in children, whereas systemic mastocytosis is the most common form of the disease in adults. Therefore, different diagnostic algorithms have to be applied in adult patients and children with suspected mastocytosis. This comprehensive review presents currently defined variants of the disease and recommendations to facilitate diagnostic work-up in children and adults with suspected mastocytosis in daily clinical practice.
Topics: Adult; Age of Onset; Child; Diagnosis, Differential; Humans; Mastocytosis, Cutaneous; Mastocytosis, Systemic; Predictive Value of Tests; Prognosis
PubMed: 26270728
DOI: 10.2340/00015555-2210 -
International Journal of Molecular... Mar 2021Pediatric mastocytosis is a heterogeneous disease characterized by accumulation of mast cells in the skin and less frequently in other organs. Somatic or germline... (Review)
Review
Pediatric mastocytosis is a heterogeneous disease characterized by accumulation of mast cells in the skin and less frequently in other organs. Somatic or germline mutations in the proto-oncogene are detected in most patients. Cutaneous mastocytosis is the most common form of the disease in children. In the majority of cases, skin lesions regress spontaneously around puberty. However, in few patients, mastocytosis is not a self-limiting disease, but persists into adulthood and can show signs of systemic involvement, especially when skin lesions are small-sized and monomorphic. Children with mastocytosis often suffer from mast cell mediator-related symptoms. Severe hypersensitivity reactions can also occur, mostly in patients with extensive skin lesions and blistering. In a substantial number of these cases, the triggering factor of anaphylaxis remains unidentified. Management of pediatric mastocytosis is mainly based on strict avoidance of triggers, treatment with H1 and H2 histamine receptor blockers, and equipment of patients and their families with epinephrine auto-injectors for use in severe anaphylactic reactions. Advanced systemic mastocytosis occurs occasionally. All children with mastocytosis require follow-up examinations. A bone marrow investigation is performed when advanced systemic mastocytosis is suspected and has an impact on therapy or when cutaneous disease persists into adulthood.
Topics: Child; Epinephrine; Histamine H1 Antagonists; Histamine H2 Antagonists; Humans; Mast Cells; Mastocytosis, Cutaneous; Mastocytosis, Systemic; Proto-Oncogene Mas; Skin
PubMed: 33806685
DOI: 10.3390/ijms22052586 -
Actas Dermo-sifiliograficas Jul 2021
Topics: Humans; Mast Cells; Mastocytosis, Cutaneous
PubMed: 33901482
DOI: 10.1016/j.ad.2021.01.004 -
International Journal of Molecular... Mar 2021Mastocytosis is characterized by the pathological accumulation of mast cells (MC) in various organs. In these patients, MC may degranulate and thereby contribute to... (Review)
Review
Mastocytosis is characterized by the pathological accumulation of mast cells (MC) in various organs. In these patients, MC may degranulate and thereby contribute to clinical symptoms, especially when a concomitant allergy is present. However, MC activation can not only be induced by high-affinity receptors for IgE, but also by anaphylatoxins, neuropeptides, IgG immune complexes, complement-components, drugs, products of bacteria or parasites, as well as physical factors such as heat, cold, vibration, stress, sun, or physical effort. Symptoms due to mediators released by activated MC may develop in adults suffering from systemic mastocytosis, but also evolve in children who usually have cutaneous mastocytosis (CM). Clinically, CM is otherwise characterized by typical brown, maculopapular skin lesions or mastocytoma associated with a positive Darier's sign. Pruritus and flushing are common and blistering may also be recorded, especially in diffuse CM (DCM). Pediatric patients with mastocytosis may also have gastrointestinal, respiratory, and neurologic complaints. Although anaphylaxis is not a typical finding, pediatric patients with massive skin involvement and high tryptase levels have a relatively high risk to develop anaphylaxis. This paper reviews MC mediator-related symptoms and anaphylaxis in children with mastocytosis, with special emphasis on risk factors, triggers, and management.
Topics: Administration, Topical; Adult; Anaphylaxis; Child; Humans; Insect Bites and Stings; Mast Cells; Mastocytosis; Mastocytosis, Systemic; Risk Factors; Skin; Tryptases
PubMed: 33799959
DOI: 10.3390/ijms22052684 -
Actas Dermo-sifiliograficas 2016Mastocytosis is a term used to describe a heterogeneous group of disorders characterized by clonal proliferation of mast cells in various organs. The organ most often... (Review)
Review
Mastocytosis is a term used to describe a heterogeneous group of disorders characterized by clonal proliferation of mast cells in various organs. The organ most often affected is the skin. Mastocytosis is a relatively rare disorder that affects both sexes equally. It can occur at any age, although it tends to appear in the first decade of life, or later, between the second and fifth decades. Our understanding of the pathophysiology of mastocytosis has improved greatly in recent years, with the discovery that somatic c-kit mutations and aberrant immunophenotypic features have an important role. The clinical manifestations of mastocytosis are diverse, and skin lesions are the key to diagnosis in most patients.
Topics: Female; Humans; Male; Mast Cells; Mastocytosis; Proto-Oncogene Proteins c-kit; Skin
PubMed: 26546030
DOI: 10.1016/j.ad.2015.09.007 -
Blood Aug 2008Mast cells have been recognized for well over 100 years. With time, human mast cells have been documented to originate from CD34+ cells, and have been implicated in host... (Review)
Review
Mast cells have been recognized for well over 100 years. With time, human mast cells have been documented to originate from CD34+ cells, and have been implicated in host responses in both innate and acquired immunity. In clinical immunology, they are recognized for their central role in IgE-mediated degranulation and allergic inflammation by virtue of their expression of the high-affinity receptor for IgE and release of potent proinflammatory mediators. In hematology, the clinical disease of mastocytosis is characterized by a pathologic increase of mast cells in tissues, often associated with mutations in KIT, the receptor for stem cell factor. More recently, and with increased understanding of how human mast cells are activated through receptors including the high-affinity receptor for IgE and KIT, specific tyrosine kinase inhibitors have been identified with the potential to interrupt signaling pathways and thus limit the proliferation of mast cells as well as their activation through immunoglobulin receptors.
Topics: Animals; Humans; Inflammation; Mast Cells; Mastocytosis; Signal Transduction
PubMed: 18684881
DOI: 10.1182/blood-2007-11-078097