Evolutionary dynamics in the years preceding acute myeloid leukaemia

According to Nature, somatic evolution in ageing tissues underlies many cancers, but our quantitative understanding of pre-cancerous evolution remains incomplete. Researchers exploited a unique collection of serial blood samples collected annually for up to a decade and beginning as early as 15 years before the diagnosis of acute myeloid leukaemia. This material provided a quantitative description of pre-cancerous evolutionary dynamics. Using deep duplex sequencing and evolutionary theory, scientists quantified 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, while the blood remains highly polyclonal. These early slow-growing clones subsequently acquire multiple further driver mutations. These later mutations confer selective advantages up to 100-fold larger than the early drivers according to Nature. Faster-growing clones harbouring multiple driver mutations can cause complete somatic sweeps of the blood decades before diagnosis. Nature reported that this feature is strongly associated with future acute myeloid leukaemia.

The data show that the clonal dynamics of blood are consistent with a set of remarkably simple evolutionary rules. These rules strike a balance between chance and determinism as described in the source text. Nature noted that the study utilized serial blood samples collected annually for up to a decade, starting as early as 15 years before acute myeloid leukaemia diagnosis.