Germline risk of clonal haematopoiesis
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In this paper, the authors synthesize what is currently known about how inherited variation shapes the risk of clonal haematopoiesis and how this genetic architecture intersects with the biology of diseases that occur with ageing.Abstract:
Clonal haematopoiesis (CH) is a common, age-related expansion of blood cells with somatic mutations that is associated with an increased risk of haematological malignancies, cardiovascular disease and all-cause mortality. CH may be caused by point mutations in genes associated with myeloid neoplasms, chromosomal copy number changes and loss of heterozygosity events. How inherited and environmental factors shape the incidence of CH is incompletely understood. Even though the several varieties of CH may have distinct phenotypic consequences, recent research points to an underlying genetic architecture that is highly overlapping. Moreover, there are numerous commonalities between the inherited variation associated with CH and that which has been linked to age-associated biomarkers and diseases. In this Review, we synthesize what is currently known about how inherited variation shapes the risk of CH and how this genetic architecture intersects with the biology of diseases that occur with ageing.read more
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Journal ArticleDOI
Somatic Mutations in Cardiovascular Disease
TL;DR: In this article , the authors provide an overview of somatic mutations and their contributions to CVD, focusing on the most common and well-described manifestation, clonal hematopoiesis of indeterminate potential.
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Loss of Y and clonal hematopoiesis in blood-two sides of the same coin?
Viktor Ljungström,Viktor Ljungström,Jonas Mattisson,Jonatan Halvardson,Tatjana Pandzic,Tatjana Pandzic,Hanna Davies,Edyta Rychlicka-Buniowska,Marcus Danielsson,Paul Lacaze,Lucia Cavelier,Lucia Cavelier,Jan P. Dumanski,Jan P. Dumanski,Panagiotis Baliakas,Panagiotis Baliakas,Lars Forsberg,Lars Forsberg +17 more
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Clonal Hematopoiesis, Somatic Mosaicism, and Age-Associated Disease.
Megan A Evans,Kenneth Walsh +1 more
TL;DR: An up-to-date review of clonal hematopoiesis within the context somatic mosaicism and aging is provided and recent epidemiological studies which have reported associations with age-related disease are described.
Journal ArticleDOI
Modeling clonal hematopoiesis in umbilical cord blood cells by CRISPR/Cas9.
Friederike Christen,Raphael Hablesreiter,Kaja Hoyer,Cornelius Hennch,Antje Maluck-Böttcher,Angela Segler,Annett Madadi,Mareike Frick,Mareike Frick,Lars Bullinger,Lars Bullinger,Franziska Briest,Frederik Damm,Frederik Damm +13 more
TL;DR: In this paper, site-specific mutations were introduced in defined regions of DNMT3A, TET2, and ASXL1 in CD34+ progenitor cells that were subsequently analyzed in short-term as well as long-term in vitro culture assays to assess self-renewal and differentiation capacities.
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Germline CHEK2 and ATM Variants in Myeloid and Other Hematopoietic Malignancies
TL;DR: The role that deleterious germline CHEK2 and ATM variants play in the development of hematopoietic malignancies is reviewed, and how this influences clinical practice, including cancer screening, hematoplastic stem cell transplantation, and therapy choice is reviewed.
References
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Journal Article
p53, CHK2, and CHK1 genes in Finnish families with Li-Fraumeni syndrome: further evidence of CHK2 in inherited cancer predisposition.
Pia Vahteristo,Anitta Tamminen,Petteri Karvinen,Hannaleena Eerola,Carita Eklund,Lauri A. Aaltonen,Carl Blomqvist,Kristiina Aittomäki,Heli Nevanlinna +8 more
TL;DR: The cancer phenotype in theCHK2-families was not characteristic of LFS, and may indicate variable phenotypic expression in the rare families with CHK2 mutations, as additional work is necessary to completely unravel the molecular background of L FS.
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Incidence, Presentation, and Prognosis of Malignancies in Ataxia-Telangiectasia: A Report From the French National Registry of Primary Immune Deficiencies
Felipe Suarez,Nizar Mahlaoui,Danielle Canioni,Chantal Andriamanga,Catherine Dubois d'Enghien,Nicole Brousse,Jean-Philippe Jais,Alain Fischer,Olivier Hermine,Dominique Stoppa-Lyonnet +9 more
TL;DR: B-cell NHL, HL, and acute lymphoblastic leukemia occur at a high rate and earlier age than carcinomas in AT and T-PLLs are rarer than initially reported.
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Aberrations of the MRE11-RAD50-NBS1 DNA damage sensor complex in human breast cancer: MRE11 as a candidate familial cancer-predisposing gene.
Jirina Bartkova,Johanna Tommiska,Lenka Oplustilova,Kirsimari Aaltonen,Anitta Tamminen,Tuomas Heikkinen,Martin Mistrik,Kristiina Aittomäki,Carl Blomqvist,Päivi Heikkilä,Jiri Lukas,Heli Nevanlinna,Jiri Bartek +12 more
TL;DR: It is proposed that germline mutations qualify MRE11 as a novel candidate breast cancer susceptibility gene in a subset of non‐BRCA1/2 families and have implications for the concept of the DNA damage response as an intrinsic anti‐cancer barrier.
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Smoking is associated with mosaic loss of chromosome Y
Jan P. Dumanski,Jan P. Dumanski,Chiara Rasi,Chiara Rasi,Mikael Lönn,Hanna Davies,Hanna Davies,Martin Ingelsson,Vilmantas Giedraitis,Lars Lannfelt,Patrik K. E. Magnusson,Cecilia M. Lindgren,Cecilia M. Lindgren,Andrew P. Morris,Andrew P. Morris,David Cesarini,Magnus Johannesson,Eva Tiensuu Janson,Lars Lind,Nancy L. Pedersen,Erik Ingelsson,Erik Ingelsson,Lars Forsberg,Lars Forsberg +23 more
TL;DR: It is demonstrated here that smoking is associated with LOY in blood cells in three independent cohorts, and the finding that smoking induces LOY thus links a preventable risk factor with the most common acquired human mutation.
Journal ArticleDOI
Macrophage Inflammation, Erythrophagocytosis, and Accelerated Atherosclerosis in Jak2 V617F Mice.
Wei Wang,Wenli Liu,Wenli Liu,Trevor P. Fidler,Ying Wang,Yang Tang,Brittany Woods,Carrie L. Welch,Bishuang Cai,Carlos Silvestre-Roig,Ding Ai,Yong-Guang Yang,Andrés Hidalgo,Andrés Hidalgo,Oliver Soehnlein,Oliver Soehnlein,Ira Tabas,Ross L. Levine,Alan R. Tall,Nan Wang +19 more
TL;DR: Hematopoietic Jak2VF expression promotes early lesion formation and increased complexity in advanced atherosclerosis, likely contributing to plaque instability.