Pathogenic and diagnostic relevance of KIT in primary mast cell activation disorders

Muñoz‐González, Javier I.; García‐Montero, Andrés C.; Órfão, Alberto; Álvarez‐Twose, Iván

doi:10.1016/j.anai.2021.07.014

Cited by 6 publications

(3 citation statements)

References 92 publications

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“…In fact, constitutive activation of KIT causes preferential differentiation of HSC toward cell lines regulated by KIT expression and signalling (mainly MCs and to a large extent also other myeloid lineages). The fact that MCs are the only haematopoietic cells that express KIT throughout their maturation [18,19] would explain why this KIT-activating mutation induces the expansion and accumulation of pathological MCs in different organs and tissues, as typically observed in SM and other KIT-mutated MC diseases [23]. Of note, the prevalence of the KIT D816V mutation is very similar among adult patients diagnosed with Non-AdvSM and AdvSM [9].…”

Section: Kit D816v Mutationmentioning

confidence: 91%

Comprehensive Analysis of Acquired Genetic Variants and Their Prognostic Impact in Systemic Mastocytosis

González‐López

Muñoz‐González

Órfão

et al. 2022

Cancers

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Systemic mastocytosis (SM) is a rare clonal haematopoietic stem cell disease in which activating KIT mutations (most commonly KIT D816V) are present in virtually every (>90%) adult patient at similar frequencies among non-advanced and advanced forms of SM. The KIT D816V mutation is considered the most common pathogenic driver of SM. Acquisition of this mutation early during haematopoiesis may cause multilineage involvement of haematopoiesis by KIT D816V, which has been associated with higher tumour burden and additional mutations in other genes, leading to an increased rate of transformation to advanced SM. Thus, among other mutations, alterations in around 30 genes that are also frequently mutated in other myeloid neoplasms have been reported in SM cases. From these genes, 12 (i.e., ASXL1, CBL, DNMT3A, EZH2, JAK2, KRAS, NRAS, SF3B1, RUNX1, SF3B1, SRSF2, TET2) have been recurrently reported to be mutated in SM. Because of all the above, assessment of multilineage involvement of haematopoiesis by the KIT D816V mutation, in the setting of multi-mutated haematopoiesis as revealed by a limited panel of genes (i.e., ASXL1, CBL, DNMT3A, EZH2, NRAS, RUNX1 and SRSF2) and associated with a poorer patient outcome, has become of great help to identify SM patients at higher risk of disease progression and/or poor survival who could benefit from closer follow-up and eventually also early cytoreductive treatment.

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Section: Kit D816v Mutationmentioning

confidence: 91%

Comprehensive Analysis of Acquired Genetic Variants and Their Prognostic Impact in Systemic Mastocytosis

González‐López

Muñoz‐González

Órfão

et al. 2022

Cancers

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“…The ideal next step after diagnosis is to obtain MCD specialist care at CoE/RC, 39,41,42 which is currently unavailable in many locations globally. Expert care may be centralized (eg, Mexico); travel, cost, and appointment availability may be barriers to care.…”

Section: Diagnosis and Health Care: Issuesmentioning

confidence: 99%

Mast Cell Diseases in Practice and Research: Issues and Perspectives Raised by Patients and Their Recommendations to the Scientific Community and Beyond

Jennings

Finnerty

Hobart³

et al. 2022

The Journal of Allergy and Clinical Immunology: In Practice

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“…51 Systemic mastocytosis is diagnosed in over 95% of the cases, and usually persists for a longer time due to a gain-of-function mutation in the KIT gene, resulting in abnormal proliferation of clonal mast cells in various organs. 52 The mutation is found in the gene coding KIT D816V tyrosine receptor kinase (cluster of differentiation 117), 53 and can lead to increased and prolonged activation of the mutated mast cells as a result of abnormal apoptosis and proliferation. 4 The prevalence of systemic mastocytosis in Europe is 0.3-13.0:100,000, 54 affecting males and females equally with unknown incidence.…”

Section: Mastocytosismentioning

confidence: 99%

Central Role of Mast Cells in Mastocytosis, Hereditary α-Tryptasemia, Mast Cell Activation Syndrome, Urticaria, and Angioedema

Rudenko¹

2022

EMJ Allergy Immunol

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Mast cells are the central cells in the pathogenesis of many conditions that are associated with mediator release. New information is emerging about the role of mast cells in a number of conditions. This review summarises current knowledge on the topic. Some conditions such as mastocytosis have a confirmed genetic background; however, the genetic background of hereditary α-tryptasemia has only recently been described, and routine testing is yet to be set up in genetic laboratories. It is still unknown whether there is a genetic predisposition leading to the development of mast cell activation syndrome as well as urticaria and angioedema, and research is under way in this direction. The best known mediator contained in mast cells is histamine 2-(4-imidazolyl)-ethylamine, but it is not the only one. The effects of other mediators are significant in mast cell-mediated conditions, and can be future therapeutic targets. Diamine oxidase deficiency is responsible for digestive issues in some people, and although not directly linked with mast cell pathology, it falls under this umbrella due to symptoms related to the effects of externally consumed histamine. Mast cell-mediated diseases are usually defined through the detection of an elevation of mast cell mediators, response to antihistamines, mast cell stabilisers, and, in some cases, anti-IgE treatment when indicated. They comprise of mastocytosis, hereditary α-tryptasemia, mast cell activation syndrome, urticaria, and angioedema.

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Pathogenic and diagnostic relevance of KIT in primary mast cell activation disorders

Cited by 6 publications

References 92 publications

Comprehensive Analysis of Acquired Genetic Variants and Their Prognostic Impact in Systemic Mastocytosis

Comprehensive Analysis of Acquired Genetic Variants and Their Prognostic Impact in Systemic Mastocytosis

Mast Cell Diseases in Practice and Research: Issues and Perspectives Raised by Patients and Their Recommendations to the Scientific Community and Beyond

Central Role of Mast Cells in Mastocytosis, Hereditary α-Tryptasemia, Mast Cell Activation Syndrome, Urticaria, and Angioedema

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