Glasgow researchers discover way to overcome chemotherapy-resistant leukaemia

Treatment-resistance in patients with one of the most aggressive types of blood cancer may be overcome by combining a new targeted drug called venetoclax with chemotherapy, researchers at the University of Glasgow have shown.

Testing for activity of a cancer gene called ‘Trib2’ in patients with acute myeloid leukaemia (AML) could identify those people who would most benefit from this targeted treatment.

AML is a highly aggressive form of blood cancer in which immature white blood cells rapidly grow out of control, restricting the production of healthy blood cells. Over 2,400 people are diagnosed with AML each year in the UK. Intensive chemotherapy, followed by a stem cell transplant, currently offers the best chance of a long term cure. But some people are unable to tolerate this treatment, or do not respond, and many more will relapse.

Researchers found that increased activity of a gene called Trib2 is responsible for the development of particularly chemotherapy-resistant leukaemia cells in around a quarter of AML patients. Trib2 switches on the production of BCL2 proteins, which promote cell survival and regulate against cell death. The BCL2 protein has been linked to treatment resistance in other types of cancer, including lymphoma, breast cancer and prostate cancer.

The Trib2 gene affects different cells in different ways and in some cells it is known to actually protect against cancer development. By switching the Trib2 gene on and off in different types of healthy blood cells grown in the lab and in mice, the researchers were able to identify the most likely original blood stem cells from which chemotherapy-resistant Trib2-driven AML develops.

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