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Nature

Blood cell takeovers linked to future acute myeloid leukemia

Later cancer-promoting mutations were linked to growth advantages up to 100-fold larger than those of early mutations in blood cell families.

Paper by Caroline J. Watson, Gladys Y. P. Poon, Hamish A. J. MacGregor, +7 more authorsJamie R. Blundell
Figure 1. Deep sequencing of serial blood samples in the years preceding AML.
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Figure 1. Deep sequencing of serial blood samples in the years preceding AML.Deep sequencing of serial blood samples in the years preceding AML.Watson et al., CC BY

Our read

Mechanisms
Studied:
Cohort study of 420,054 UK Biobank participants, against all other participants
What changed:
Future myeloid leukemia was more common with blood-cell takeovers than without: 42 prospective cases among 388 participants with takeovers
The catch:
Filtering inherited variants can also remove blood-cell takeovers from detection

Editor of record: Boris Djordjevic · AgingResearch.News

Paper
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Forty-seven postmenopausal women, aged 50–74 at enrollment, who later developed acute myeloid leukemia, a blood cancer, provided samples for a longitudinal analysis with matched controls. Blood samples were collected annually for up to a decade, beginning as early as 15 years before diagnosis.

Using DNA sequencing and evolutionary models, researchers estimated that the first cancer-promoting mutations typically arose in the first few decades of life, when many distinct cell families coexisted in the blood. These slow-growing families—groups descended from one cell—later acquired additional mutations linked to larger growth advantages. Faster-growing families carrying several mutations could completely take over the blood decades before diagnosis. These takeovers were strongly associated with future acute myeloid leukemia.

Why it matters

The evolution of aging blood is part of how cancers arise. This work offers a framework for understanding how chance and competitive growth shape the long path toward leukemia.

Caveats

The early mutation dates and growth advantages were inferred using mathematical models fitted to later-life samples. The longitudinal sample comprised postmenopausal women, so the same patterns may not apply to men or younger women.

From the paper

Participants

A total of 516 individuals were identified who were diagnosed with myeloid leukaemia (ICD-10 C92) after the UK Biobank baseline assessment (‘prospective cases’).

Methods, High VAF variants in the UK Biobank

Quoted word for word from the full text on nature.com.

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