Clinical Impact of Inherited and Acquired Genetic Variants in Mastocytosis
Mastocytosis is a rare and complex disease characterized by expansion of clonal mast cells (MC) in skin and/or various internal organ systems. Involvement of internal organs leads to the diagnosis of systemic mastocytosis (SM). The WHO classification divides SM into indolent SM, smoldering SM and ad...
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doaj-d302c35eb80740d6a905e2c66160ba182021-01-03T00:01:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-012241141110.3390/ijms22010411Clinical Impact of Inherited and Acquired Genetic Variants in MastocytosisBoguslaw Nedoszytko0Michel Arock1Jonathan J. Lyons2Guillaume Bachelot3Lawrence B. Schwartz4Andreas Reiter5Mohamad Jawhar6Juliana Schwaab7Magdalena Lange8Georg Greiner9Gregor Hoermann10Marek Niedoszytko11Dean D. Metcalfe12Peter Valent13Department of Dermatology, Allergology and Venereology, Medical University of Gdansk, 80-211 Gdansk, PolandDepartment of Hematology, APHP, Hôpital Pitié-Salpêtrière and Sorbonne University, 75013 Paris, FranceLaboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-188, USADepartment of Hematology, APHP, Hôpital Pitié-Salpêtrière and Sorbonne University, 75013 Paris, FranceDepartment of Internal Medicine, Division of Rheumatology, Allergy & Immunology, Virginia Commonwealth University, Richmond, VA 23298, USAUniversity Hospital Mannheim, Heidelberg University, 68167 Mannheim, GermanyUniversity Hospital Mannheim, Heidelberg University, 68167 Mannheim, GermanyUniversity Hospital Mannheim, Heidelberg University, 68167 Mannheim, GermanyDepartment of Dermatology, Allergology and Venereology, Medical University of Gdansk, 80-211 Gdansk, PolandDepartment of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, AustriaLudwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Allergology, Medical University of Gdansk, 80-211 Gdansk, PolandLaboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-188, USALudwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, 1090 Vienna, AustriaMastocytosis is a rare and complex disease characterized by expansion of clonal mast cells (MC) in skin and/or various internal organ systems. Involvement of internal organs leads to the diagnosis of systemic mastocytosis (SM). The WHO classification divides SM into indolent SM, smoldering SM and advanced SM variants, including SM with an associated hematologic neoplasm, aggressive SM, and MC leukemia. Historically, genetic analysis of individuals with pure cutaneous mastocytosis (CM) and SM have focused primarily on cohort studies of inherited single nucleotide variants and acquired pathogenic variants. The most prevalent pathogenic variant (mutation) in patients with SM is <i>KIT</i> p.D816V, which is detectable in most adult patients. Other somatic mutations have also been identified—especially in advanced SM—in <i>TET2</i>, <i>SRSF2</i>, <i>ASXL1</i>, <i>RUNX1</i>, <i>CBL</i> and <i>JAK2</i>, and shown to impact clinical and cellular phenotypes. Although only small patient cohorts have been analyzed, disease associations have also been identified in several germline variants within genes encoding certain cytokines or their receptors (<i>IL13</i>, <i>IL6</i>, <i>IL6R</i>, <i>IL31</i>, <i>IL4R</i>) and toll-like receptors. More recently, an increased prevalence of hereditary alpha-tryptasemia (HαT) caused by increased <i>TPSAB1</i> copy number encoding alpha-tryptase has been described in patients with SM. Whereas HαT is found in 3–6% of general Western populations, it is identified in up to 17% of patients with SM. In the current manuscript we review the prevalence, functional role and clinical impact of various germline and somatic genetic variants in patients with mastocytosis.https://www.mdpi.com/1422-0067/22/1/411mast cellsmast cell activation syndromegene polymorphismsprognosticationhereditary alpha-tryptasemia<i>KIT</i> variants |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Boguslaw Nedoszytko Michel Arock Jonathan J. Lyons Guillaume Bachelot Lawrence B. Schwartz Andreas Reiter Mohamad Jawhar Juliana Schwaab Magdalena Lange Georg Greiner Gregor Hoermann Marek Niedoszytko Dean D. Metcalfe Peter Valent |
spellingShingle |
Boguslaw Nedoszytko Michel Arock Jonathan J. Lyons Guillaume Bachelot Lawrence B. Schwartz Andreas Reiter Mohamad Jawhar Juliana Schwaab Magdalena Lange Georg Greiner Gregor Hoermann Marek Niedoszytko Dean D. Metcalfe Peter Valent Clinical Impact of Inherited and Acquired Genetic Variants in Mastocytosis International Journal of Molecular Sciences mast cells mast cell activation syndrome gene polymorphisms prognostication hereditary alpha-tryptasemia <i>KIT</i> variants |
author_facet |
Boguslaw Nedoszytko Michel Arock Jonathan J. Lyons Guillaume Bachelot Lawrence B. Schwartz Andreas Reiter Mohamad Jawhar Juliana Schwaab Magdalena Lange Georg Greiner Gregor Hoermann Marek Niedoszytko Dean D. Metcalfe Peter Valent |
author_sort |
Boguslaw Nedoszytko |
title |
Clinical Impact of Inherited and Acquired Genetic Variants in Mastocytosis |
title_short |
Clinical Impact of Inherited and Acquired Genetic Variants in Mastocytosis |
title_full |
Clinical Impact of Inherited and Acquired Genetic Variants in Mastocytosis |
title_fullStr |
Clinical Impact of Inherited and Acquired Genetic Variants in Mastocytosis |
title_full_unstemmed |
Clinical Impact of Inherited and Acquired Genetic Variants in Mastocytosis |
title_sort |
clinical impact of inherited and acquired genetic variants in mastocytosis |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-01-01 |
description |
Mastocytosis is a rare and complex disease characterized by expansion of clonal mast cells (MC) in skin and/or various internal organ systems. Involvement of internal organs leads to the diagnosis of systemic mastocytosis (SM). The WHO classification divides SM into indolent SM, smoldering SM and advanced SM variants, including SM with an associated hematologic neoplasm, aggressive SM, and MC leukemia. Historically, genetic analysis of individuals with pure cutaneous mastocytosis (CM) and SM have focused primarily on cohort studies of inherited single nucleotide variants and acquired pathogenic variants. The most prevalent pathogenic variant (mutation) in patients with SM is <i>KIT</i> p.D816V, which is detectable in most adult patients. Other somatic mutations have also been identified—especially in advanced SM—in <i>TET2</i>, <i>SRSF2</i>, <i>ASXL1</i>, <i>RUNX1</i>, <i>CBL</i> and <i>JAK2</i>, and shown to impact clinical and cellular phenotypes. Although only small patient cohorts have been analyzed, disease associations have also been identified in several germline variants within genes encoding certain cytokines or their receptors (<i>IL13</i>, <i>IL6</i>, <i>IL6R</i>, <i>IL31</i>, <i>IL4R</i>) and toll-like receptors. More recently, an increased prevalence of hereditary alpha-tryptasemia (HαT) caused by increased <i>TPSAB1</i> copy number encoding alpha-tryptase has been described in patients with SM. Whereas HαT is found in 3–6% of general Western populations, it is identified in up to 17% of patients with SM. In the current manuscript we review the prevalence, functional role and clinical impact of various germline and somatic genetic variants in patients with mastocytosis. |
topic |
mast cells mast cell activation syndrome gene polymorphisms prognostication hereditary alpha-tryptasemia <i>KIT</i> variants |
url |
https://www.mdpi.com/1422-0067/22/1/411 |
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