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Peer-reviewedCC BYNature

Evolutionary dynamics in the years preceding acute myeloid leukaemia

  • Caroline J. Watson1
  • Gladys Y. P. Poon1
  • Hamish A J MacGregor1
  • Adriana V.A. Fonseca1
  • Sophia Apostolidou2,3
  • Aristi Damaskou2,3
  • Christopher T. Boniface2,3
  • Samuel Hackett1
  • Aleksandra Gentry‐Maharaj
  • Usha Menon
  • Jamie R. Blundell
  1. 1University of Cambridge
  2. 2MRC Clinical Trials Unit at UCL
  3. 3University College London
Open at sourceDOICite

Abstract

Somatic evolution in ageing tissues underlies many cancers 1,2 . However, our quantitative understanding of the rules governing this pre-cancerous evolution remains incomplete. Here we exploit a unique collection of serial blood samples 3 , collected annually for up to a decade and beginning as early as 15 years before diagnosis of acute myeloid leukaemia, to provide a quantitative description of pre-cancerous evolutionary dynamics. Using deep duplex sequencing and evolutionary theory, we quantify the acquisition ages and fitness effects of the key driver events in acute myeloid leukaemia development. The first driver mutations are typically acquired in the first few decades of life, when the blood remains highly polyclonal. These early slow-growing clones subsequently acquire multiple further driver mutations that confer selective advantages up to 100-fold larger than the early drivers. These faster-growing clones harbouring multiple driver mutations can cause complete somatic sweeps of the blood decades before diagnosis, a feature strongly associated with future acute myeloid leukaemia. Our data show that the clonal dynamics of blood are consistent with a set of remarkably simple evolutionary rules that strike a balance between chance and determinism.

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Cite

BibTeXRIS
BibTeX
@article{watson2026evolutionary,
  title = {{Evolutionary dynamics in the years preceding acute myeloid leukaemia}},
  author = {Caroline J. Watson and Gladys Y. P. Poon and Hamish A J MacGregor and Adriana V.A. Fonseca and Sophia Apostolidou and Aristi Damaskou and Christopher T. Boniface and Samuel Hackett and Aleksandra Gentry‐Maharaj and Usha Menon and Jamie R. Blundell},
  journal = {Nature},
  year = {2026},
  month = nov,
  doi = {10.1038/s41586-026-11269-x},
  url = {https://doi.org/10.1038/s41586-026-11269-x},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Evolutionary dynamics in the years preceding acute myeloid leukaemia
AU  - Caroline J. Watson
AU  - Gladys Y. P. Poon
AU  - Hamish A J MacGregor
AU  - Adriana V.A. Fonseca
AU  - Sophia Apostolidou
AU  - Aristi Damaskou
AU  - Christopher T. Boniface
AU  - Samuel Hackett
AU  - Aleksandra Gentry‐Maharaj
AU  - Usha Menon
AU  - Jamie R. Blundell
PY  - 2026
DA  - 2026/11/11
JO  - Nature
DO  - 10.1038/s41586-026-11269-x
UR  - https://doi.org/10.1038/s41586-026-11269-x
AB  - Somatic evolution in ageing tissues underlies many cancers 1,2 . However, our quantitative understanding of the rules governing this pre-cancerous evolution remains incomplete. Here we exploit a unique collection of serial blood samples 3 , collected annually for up to a decade and beginning as early as 15 years before diagnosis of acute myeloid leukaemia, to provide a quantitative description of pre-cancerous evolutionary dynamics. Using deep duplex sequencing and evolutionary theory, we quantify the acquisition ages and fitness effects of the key driver events in acute myeloid leukaemia development. The first driver mutations are typically acquired in the first few decades of life, when the blood remains highly polyclonal. These early slow-growing clones subsequently acquire multiple further driver mutations that confer selective advantages up to 100-fold larger than the early drivers. These faster-growing clones harbouring multiple driver mutations can cause complete somatic sweeps of the blood decades before diagnosis, a feature strongly associated with future acute myeloid leukaemia. Our data show that the clonal dynamics of blood are consistent with a set of remarkably simple evolutionary rules that strike a balance between chance and determinism.
SN  - 0028-0836
SN  - 1476-4687
ER  -