Evolutionary dynamics in the years preceding acute myeloid leukaemia.

Multiple-driver clones in blood can undergo complete somatic sweeps up to decades before acute myeloid leukaemia, with selective advantages up to 100-fold over early driver mutations.

• Why it matters: Quantitative rules for how pre-cancerous somatic evolution unfolds in ageing blood are incomplete, limiting understanding of when and how acute myeloid leukaemia emerges.
• What they did: Annual serial blood samples collected for up to a decade, starting as early as 15 years before diagnosis, were analyzed using deep duplex sequencing and evolutionary theory to estimate acquisition ages and fitness effects of key driver events.
• The result: Early driver mutations arise in highly polyclonal blood in the first few decades, then later multi-driver clones expand with strong selective advantages, and complete sweeps are strongly associated with future acute myeloid leukaemia.

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