How leukemia cells outsmart key treatments over time

If you or someone you know has heard of acute myeloid leukemia (AML), you probably know it is a serious blood cancer that mostly affects older adults. Doctors often use special medicines called hypomethylating agents, like decitabine and azacitidine, to treat AML when patients cannot get very strong chemotherapy. But even when these treatments help at first, the cancer almost always finds ways to fight back. Scientists have been working hard to discover exactly how this resistance happens, and the latest research gives us important clues.

Why do leukemia cells become resistant?

When doctors use decitabine to treat AML, some patients respond well at first. Over time, though, the cancer cells can change, making the medicine less effective. A recent study investigated this process by looking at AML patients who had received several cycles of decitabine and then experienced a relapse or worsening of their cancer (Genetic and epigenetic alterations at secondary resistance after continued decitabine-based treatment of acute myeloid leukemia).

The researchers took samples from these patients before starting treatment and again after their cancer became resistant. By closely examining the DNA of the cancer cells, they found that the number of genetic mutations increased over time. This means the leukemia cells are constantly changing, and some of those changes help them survive despite the medication.

Key genetic changes in resistant leukemia cells

One important discovery was that many patients developed new mutations in genes that are already known to play a role in cancer. For example, some patients gained mutations in the IDH1 gene, which might open up new treatment options using targeted medicines called IDH1 inhibitors. Others developed changes in genes like DCK, which helps activate decitabine inside the cells. When DCK is altered, decitabine might not work as well. These findings echo earlier research showing that the way our cells handle medicines can change through mutations (Decitabine and 5-azacytidine resistance emerges from adaptive responses of the pyrimidine metabolism network).

The discovery of DCK mutations as a possible cause for resistance is especially interesting, as it suggests that switching to another medicine like azacitidine—activated by a different enzyme—could help some patients.

Epigenetic changes: More than just DNA mutations

But resistance is not just about DNA changes. The scientists also studied something called DNA methylation, which is a way cells can turn genes on or off without changing the actual DNA code. After months of decitabine treatment, they found that certain DNA sites lost their methylation marks, a sign that the cancer’s biology is changing in response to the medicine. Some of these changes happened in genes involved in moving ions (like zinc) in and out of cells, which might be important for how leukemia grows.

If you are interested in how cancer treatments can change blood cells over time, you might enjoy reading about how chemotherapy affects blood stem cells in this SlothMD article.

Not all resistance is the same: Personalized approaches

A striking result from the study is that there is no single way AML becomes resistant. Each patient’s cancer developed a unique set of mutations and changes. This finding supports the idea that future cancer care could be much more personalized, using health AI tools to match the right treatments to each patient’s cancer genetics. If you are curious about how scientists use health AI to personalize cancer care, check out this SlothMD article about ovarian cancer research.

What it means for patients

Understanding why AML cells become resistant to decitabine and similar medicines can help doctors develop new strategies. For example, if a patient’s cancer develops a DCK mutation, switching to a different medicine or adding a targeted drug might help. The research also hints that some changes seen in resistant leukemia cells might not make them more sensitive to certain new drugs, so it is important to test these ideas carefully before trying them in patients.

Looking to the future

Although this research did not find one universal cause of resistance, it provided a much clearer picture of the many ways AML cells can adapt. Scientists hope that by tracking these changes, they can stay one step ahead and design better treatments that keep working longer. As health AI and genetic testing become more common, doctors will have more tools to find the right therapy for each person’s cancer, making care smarter and more effective for everyone.