The first gene changes behind a common adult leukemia often appear before age 20, decades before diagnosis, a study of stored blood finds

The first gene changes that lead to acute myeloid leukemia, or AML, often arise in childhood or early adulthood, more than 50 years before the cancer is found, according to a study published Nov. 11 in the journal Nature.  AML is a fast-moving cancer of the blood and bone marrow that mostly strikes older adults.

The finding suggests doctors might one day spot people at high risk years ahead by looking for certain mutated blood cells, the University of Cambridge-led team wrote.  Both ideas are untested, and there is no screening test for AML today.

What the researchers found

• In two-thirds of the women who later got AML, the first cancer-linked mutation was already present by age 20, the researchers estimated.
• Those early mutated cells grew slowly, taking about two to seven years to double in number.  The same kind of slow-growing cells are common in healthy older people, a condition called clonal hematopoiesis.
• Second mutations typically came about 30 years before diagnosis and made cells grow much faster, doubling every one to three years.  Each later mutation sped growth further, by up to 100 times the advantage of the first.
• In some women, a single group of mutated cells took over almost all of the blood years or decades before diagnosis, a pattern strongly tied to later leukemia.

How this could help, and whether it will be used

The main payoff is time.  Because the second and third gene changes usually arrive more than a decade before diagnosis, the authors wrote, there is “a long window of opportunity for intervention.”  Fast-growing groups of mutated cells, and blood taken over almost entirely by one group of cells, were the clearest warning signs.  The authors suggest that looking for those patterns, for example by comparing a blood sample with a cheek swab to tell inherited DNA from acquired mutations, could substantially improve predictions of who will get AML.

They also suggest that mild treatments that only slow the riskiest cells might prevent some cases, because small slowdowns add up over decades.  As one example they point to IDH inhibitors, pills that block a mutated growth enzyme, or vaccines aimed at the mutated cells.  One IDH inhibitor, enasidenib, sold as Idhifa, has been approved by the U.S. Food and Drug Administration since 2017, but only for adults whose AML has come back or stopped responding to treatment and carries an IDH2 mutation.  It is not approved to prevent leukemia, and it can cause serious side effects, the FDA says.

None of this is in use yet.  The paper does not test a screening program or a preventive drug, and the authors call these ideas speculation.  Neither idea has been tested in a clinical trial, and the study included only women.

How the study worked

The team used blood stored by a U.K. ovarian cancer screening trial that collected yearly samples from 50,640 women aged 50 to 74, starting in 2001 to 2005.  It found 47 women who later developed AML, at a median age of 72, and compared up to 10 samples from each with samples from 46 women of the same ages who stayed cancer-free.  A very accurate DNA sequencing method let them track rare mutated cells over time.  The study included only women, and the researchers did not have samples of the leukemias themselves, so they could not prove the cells they tracked became the cancer.

Source:  Watson et al., “Evolutionary dynamics in the years preceding acute myeloid leukaemia,” Nature, Nov. 11, 2026 (open access); U.S. Food and Drug Administration, Aug. 1, 2017.