In a comprehensive study of acute lymphoblastic leukaemia, researchers at Karolinska Institutet have shown that the enzyme ADK plays an important role in determining how leukaemia cells respond to triciribine. Published in npj Precision Oncology, the study also provides new insights into how the compound works and identifies ADK as a potential biomarker for predicting its effects on leukaemia cells.
Acute lymphoblastic leukaemia (ALL) is a blood cancer that can affect people of all ages. Triciribine is a compound that has previously been investigated as a cancer treatment, but its mechanism of action in ALL cells has not been fully understood. The researchers therefore set out to investigate how triciribine acts in leukaemia cells and why some cells are more susceptible to its effects than others.
To better understand how triciribine works, the researchers used several methods to study a large number of proteins in leukaemia cells. This allowed them to map the cellular processes affected by the compound. Their findings suggest that triciribine disrupts several processes that leukaemia cells need to grow and divide, including the production of building blocks for DNA and RNA.
One important factor was the enzyme ADK, which is required to convert triciribine into its active form inside the cell. The researchers found that triciribine had a greater effect on laboratory-grown leukaemia cells with higher levels of ADK. A similar pattern was observed in ten patient samples containing leukaemia cells exposed to triciribine outside the body.
"We found that ADK levels were associated with the effect of triciribine on leukaemia cells. This makes ADK an interesting candidate as a potential biomarker," says Xuekang Qi , researcher at the Department of Oncology-Pathology and first author of the study.
Triciribine has previously been tested in clinical trials involving patients with blood cancers, but treatment responses have been limited. The new study is based on experiments using laboratory-grown leukaemia cells and patient-derived leukaemia cells studied outside the body. It therefore remains to be established whether ADK can also predict treatment response in patients.
"If ADK proves able to predict treatment response, it could improve our ability to identify patients who may benefit from triciribine. This is particularly relevant for a compound that has produced limited treatment responses in previous clinical trials," says Rozbeh Jafari , researcher at the same department and senior author of the study.
The study was conducted by researchers at Karolinska Institutet and Science for Life Laboratory in collaboration with researchers at the Swedish University of Agricultural Sciences and Umeå University. The research was funded by, among others, the Swedish Childhood Cancer Fund, the Swedish Cancer Society, the Swedish Research Council, the Cancer Research Funds of Radiumhemmet and Karolinska Institutet's research foundations. The researchers report no conflicts of interest.
Publication
Qi X, Mermelekas G, Hodek O, Aswad L, Glaziou Q, Leo IR, Struyf N, Hormann FM, Siavelis I, Bwanika HC, Hovey OFJ, Haraldsson M, Rudd SG, Johansson AI, Erkers T, Tamm KP, Lehtiö J, Jafari R, NPJ Precision Oncology, online 10 October 2026, doi: 10.1038/s41698-026-01736-z
