Every person with acute myeloid leukemia experiences their disease differently. Some respond well to treatment; others don't. For decades, doctors have struggled to explain why. Now, a major new study suggests the answer may lie not in the genes themselves, but in how those genes are switched on and off.
Researchers at Sweden's Karolinska Institutet and Japan's Kyoto University analyzed blood samples from 1,563 patients diagnosed with acute myeloid leukemia (AML), an aggressive cancer where immature blood cells grow out of control. Rather than looking only at genetic mutations — the approach doctors have traditionally used — the team studied epigenetics: the chemical tags and mechanisms that control whether a gene is active or silent, without changing the DNA code itself.
What they found was striking. Based on patterns of gene regulation, the researchers were able to divide AML into 16 distinct subgroups, each with its own biological characteristics. "Our results show that, based on epigenetic analyses, leukemia can be divided into new biologically relevant subgroups that provide more information than genetic analyses alone," said Professor Sören Lehmann of Karolinska Institutet's Department of Medicine in Huddinge.
These subgroups weren't just biologically different — they behaved differently clinically too. Some patients in certain groups survived longer than others, and these epigenetic categories predicted outcomes more accurately than the classification systems doctors currently use. The team also tested 250 different drugs on cells from these groups and found that each subgroup responded differently to various treatments. "This suggests that epigenetic changes may also influence how patients respond to treatment," Lehmann said.
The findings, published in the journal Nature, don't replace existing genetic tests for leukemia. Instead, they add a new layer of understanding that could help doctors tailor treatment to each patient's specific cancer profile — a goal known as personalized medicine. Before that happens, though, researchers say more studies are needed to confirm the results and figure out how to use them in everyday clinical care.
The study represents a shift in how scientists think about blood cancers. By examining not just what genes are mutated, but how those genes are being regulated, doctors may one day predict more accurately which patients need aggressive treatment and which might respond to gentler therapies.