Clonal haematopoiesis harbouring AML-associated mutations is ubiquitous in healthy adults

Andrew L. Young, Grant A. Challen, Brenda M. Birmann, Todd E. Druley

Research output: Contribution to journalArticlepeer-review

330 Scopus citations


Clonal haematopoiesis is thought to be a rare condition that increases in frequency with age and predisposes individuals to haematological malignancy. Recent studies, utilizing next-generation sequencing (NGS), observed haematopoietic clones in 10% of 70-year olds and rarely in younger individuals. However, these studies could only detect common haematopoietic clones - >0.02 variant allele fraction (VAF) - due to the error rate of NGS. To identify and characterize clonal mutations below this threshold, here we develop methods for targeted error-corrected sequencing, which enable the accurate detection of clonal mutations as rare as 0.0003 VAF. We apply these methods to study serially banked peripheral blood samples from healthy 50-60-year-old participants in the Nurses' Health Study. We observe clonal haematopoiesis, frequently harbouring mutations in DNMT3A and TET2, in 95% of individuals studied. These clonal mutations are often stable longitudinally and present in multiple haematopoietic compartments, suggesting a long-lived haematopoietic stem and progenitor cell of origin.

Original languageEnglish
Article number12484
JournalNature communications
StatePublished - Aug 22 2016


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