Germline risk of clonal haematopoiesis
Reads0
Chats0
TLDR
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
Citations
More filters
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.
Journal ArticleDOI
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
Journal ArticleDOI
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.
Journal ArticleDOI
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
More filters
Journal ArticleDOI
Advances in germline predisposition to acute leukaemias and myeloid neoplasms.
TL;DR: The presumption that familial leukaemias only present in childhood is no longer true, in large part due to the numerous studies demonstrating germline DDX41 mutations in adults with MDS and AML.
Journal ArticleDOI
Germline TET2 loss of function causes childhood immunodeficiency and lymphoma.
Jarmila Stremenova Spegarova,Dylan Lawless,Siti Mardhiana Mohamad,Karin R. Engelhardt,Gina M. Doody,Jennifer Shrimpton,Anne Rensing-Ehl,Stephan Ehl,Frédéric Rieux-Laucat,Catherine Cargo,Helen Griffin,Aneta Mikulasova,Meghan Acres,Neil V. Morgan,James A. Poulter,Eamonn Sheridan,Philip Chetcuti,Sean O’Riordan,Rashida Anwar,Clive Carter,Stefan Przyborski,Kevin Windebank,Andrew J. Cant,Andrew J. Cant,Majlinda Lako,Chris M. Bacon,Chris M. Bacon,Sinisa Savic,Sophie Hambleton,Sophie Hambleton +29 more
TL;DR: These are the first reported cases of autosomal recessive germline TET2 deficiency in humans, causing clinically significant immunodeficiency and an autoimmune lymphoproliferative syndrome with marked predisposition to lymphoma.
Journal ArticleDOI
Telomeres, senescence, and hematopoietic stem cells
Stefan Zimmermann,Uwe M. Martens +1 more
TL;DR: The relevance of telomere maintenance for the hematopoietic stem cell compartment is discussed and potential functions of telomerase in this context are considered and possible clinical applications oftelomere manipulation in HSCs are presented.
Journal ArticleDOI
Fibronectin in malignancy: Cancer-specific alterations, protumoral effects, and therapeutic implications.
Jonathan Rick,Ankush Chandra,Cecilia L Dalle Ore,Alan T. Nguyen,Garima Yagnik,Manish K. Aghi +5 more
TL;DR: Fundamental studies that have investigated the impact of fibronectin in cancer are presented and it is shown that understanding the effect of this molecule has the potential to elucidate cancer biology.
Journal ArticleDOI
Clonal hematopoiesis in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis
Christopher Maximilian Arends,Marlene Weiss,Friederike Christen,Claudia Eulenberg-Gustavus,Anthony Rousselle,Ralph Kettritz,Kai-Uwe Eckardt,Willy Chan,Kaja Hoyer,Mareike Frick,Lars Bullinger,Markus Bieringer,Adrian Schreiber,Frederik Damm +13 more
TL;DR: In this paper, the authors found that the frequency of CHIP increases with age and associates with higher risk of developing hematologic malignancies and cardiovascular diseases, leading to increased overall mortality.