Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Stacey, Simon N
Norddahl, Gudmundur L
Frigge, Michael L
Magnusson, Olafur T
Thorgeirsson, Thorgeir E
Gudjonsson, Sigurjon A
Jonasson, Jon G
Gudbjartsson, Daniel F
MetadataShow full item record
CitationClonal hematopoiesis, with and without candidate driver mutations, is common in the elderly. 2017, 130 (6):742-752 Blood
AbstractClonal hematopoiesis (CH) arises when a substantial proportion of mature blood cells is derived from a single dominant hematopoietic stem cell lineage. Somatic mutations in candidate driver (CD) genes are thought to be responsible for at least some cases of CH. Using whole-genome sequencing of 11 262 Icelanders, we found 1403 cases of CH by using barcodes of mosaic somatic mutations in peripheral blood, whether or not they have a mutation in a CD gene. We find that CH is very common in the elderly, trending toward inevitability. We show that somatic mutations in TET2, DNMT3A, ASXL1, and PPM1D are associated with CH at high significance. However, known CD mutations were evident in only a fraction of CH cases. Nevertheless, the highly prevalent CH we detect associates with increased mortality rates, risk for hematological malignancy, smoking behavior, telomere length, Y-chromosome loss, and other phenotypic characteristics. Modeling suggests some CH cases could arise in the absence of CD mutations as a result of neutral drift acting on a small population of active hematopoietic stem cells. Finally, we find a germline deletion in intron 3 of the telomerase reverse transcriptase (TERT) gene that predisposes to CH (rs34002450; P = 7.4 × 10(-12); odds ratio, 1.37).
RightsArchived with thanks to Blood
- CRISPR-Mediated Gene Editing to Assess the Roles of Tet2 and Dnmt3a in Clonal Hematopoiesis and Cardiovascular Disease.
- Authors: Sano S, Oshima K, Wang Y, Katanasaka Y, Sano M, Walsh K
- Issue date: 2018 Jul 20
- <i>DNMT3A</i> and <i>TET2</i> dominate clonal hematopoiesis and demonstrate benign phenotypes and different genetic predispositions.
- Authors: Buscarlet M, Provost S, Zada YF, Barhdadi A, Bourgoin V, Lépine G, Mollica L, Szuber N, Dubé MP, Busque L
- Issue date: 2017 Aug 10
- Clonal hematopoiesis as determined by the HUMARA assay is a marker for acquired mutations in epigenetic regulators in older women.
- Authors: Wiedmeier JE, Kato C, Zhang Z, Lee H, Dunlap J, Nutt E, Rattray R, McKay S, Eide C, Press R, Mori M, Druker B, Dao KH
- Issue date: 2016 Sep
- [Clonal haematopoiesis: A concise review].
- Authors: Danlos FX, Papo M, Micol JB
- Issue date: 2019 Oct
- Atherosclerosis and clonal hematopoyesis: A new risk factor.
- Authors: Páramo Fernández JA
- Issue date: 2018 May - Jun