Serial Blood Samples Reveal Leukemia’s Evolution Decades Before Diagnosis

K. annually, with only about one in six patients surviving five years after diagnosis. Although many healthy older adults carry leukemia-associated mutations in their blood cells, relatively few develop AML, making it difficult to predict who is at risk. New research using stored blood samples collected over time has traced the development of AML years to decades before diagnosis, potentially improving early risk assessment.

Researchers at the University of Cambridge and University College London (UCL) used ultrasensitive DNA sequencing and mathematical modeling to trace the development of acute myeloid leukemia (AML) before diagnosis. By analyzing serial blood samples, the team reconstructed the evolution of cancer-driving mutations and measured the growth of mutated blood-cell populations, known as clones. The study focused on clonal hematopoiesis, in which blood cells acquire mutations also found in leukemia.

The samples came from the UK Collaborative Trial of Ovarian Cancer Screening, which collected annual blood samples from approximately 50,000 women for up to 11 years. Researchers analyzed samples from 47 women who subsequently developed AML at an average age of 72, alongside 46 matched controls who remained free of blood cancer. Some samples had been collected as early as 15 years before diagnosis, although none were obtained at the time of diagnosis.

The analysis revealed that in two-thirds of AML cases, the first cancer-driving mutation had arisen before age 20, more than 50 years before diagnosis. These early mutations were followed by decades of slow clonal expansion, with each additional mutation accelerating growth approximately two- to threefold. Cells carrying four cancer-driving mutations could double in number within weeks, demonstrating how progressively acquired mutations accelerate disease development.

In at least one-third of AML cases, a mutated clone had become dominant in the blood years before diagnosis, a process known as a somatic sweep. No such events were observed among cancer-free controls, while supporting UK Biobank data linked these sweeps to substantially increased AML risk. However, in approximately one in five cases, expanding mutated clones became detectable only one to two years before diagnosis, suggesting a shorter window for early detection in some patients. 

The findings highlight the potential of longitudinal blood testing to identify individuals at increased risk of AML before clinical symptoms emergency have a shorter warning period. The findings were published in Nature on November 11, 2026, with collaborating institutions including the University of Cambridge and UCL.

“Serial blood samples are a fossil record of the blood's evolution. They let us go back in time and reconstruct when each mutation arose and how fast it grew. What surprised us most is how predictable the growth of these clones is. Once a clone is established, its growth rate today tells you where it will be years, even decades, from now,” said Professor Jamie Blundell from the Early Cancer Institute at the University of Cambridge.

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