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Concordance for clonal hematopoiesis is limited in elderly twins

Research output: Contribution to journalArticle

Margarete Alice Fabre, Thomas McKerrell, Maximillian Zwiebel, M S Vijayabaskar, Naomi Rachel Park, Philippa M Wells, Roland Rad, Panagiotis Deloukas, Kerrin S Small, Claire J Steves, George S Vassiliou

Original languageEnglish
Pages (from-to)269-273
Number of pages5
JournalBlood
Volume135
Issue number4
Early online date25 Oct 2019
DOIs
Publication statusPublished - 23 Jan 2020

Bibliographical note

Copyright © 2019 American Society of Hematology.

King's Authors

Abstract

Although acquisition of leukemia-associated somatic mutations by 1 or more hematopoietic stem cells is inevitable with advancing age, its consequences are highly variable, ranging from clinically silent clonal hematopoiesis (CH) to leukemic progression. To investigate the influence of heritable factors on CH, we performed deep targeted sequencing of blood DNA from 52 monozygotic (MZ) and 27 dizygotic (DZ) twin pairs (aged 70-99 years). Using this highly sensitive approach, we identified CH (variant allele frequency ≥0.5%) in 62% of individuals. We did not observe higher concordance for CH within MZ twin pairs as compared with that within DZ twin pairs, or to that expected by chance. However, we did identify 2 MZ pairs in which both twins harbored identical rare somatic mutations, suggesting a shared cell of origin. Finally, in 3 MZ twin pairs harboring mutations in the same driver genes, serial blood samples taken 4 to 5 years apart showed substantial twin-to-twin variability in clonal trajectories. Our findings propose that the inherited genome does not exert a dominant influence on the behavior of adult CH and provide evidence that CH mutations may be acquired in utero.

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