Liz Burtally
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RUNX genes and their role in blood cancer development

Liz Burtally
Posted by
10 Jan 2017

Professor James Neil – one of our researchers at The University of Glasgow – sheds light on how we may be able to reverse resistance to commonly used drugs in blood cancer treatment.

A family of genes called RUNX are known to help maintain healthy blood cell formation by orchestrating the activity of other genes that are involved in the process. RUNX genes do this by encoding proteins called transcription factors, which switch other genes on and off in the right place at the right time. But like many genes important for normal development processes, the RUNX genes are also linked to human cancer.

Professor James Neil – one of our researchers at The University of Glasgow who was also recently awarded an OBE – has led the way in unravelling how RUNX genes can lead to blood cancer. Now a new study shows that we may be able to reverse resistance to commonly used drugs in blood cancer treatment by blocking the activity of RUNX genes.

The role of RUNX in blood cancer

An earlier study by Bloodwise funded researchers, led by Prof Neil, showed that RUNX genes can drive lymphoma development when their activity is higher than normal. The effect was even more potent when another cancer-causing gene called MYC is over-active at the same time. Even lymphoma cells that have normal levels of RUNX activity were 'addicted' to their influence, meaning that they strongly rely on these genes for survival.

Lymphoma cells. Credit: Wellcome.

Because RUNX genes were found to be central in blood cancer development, it opened up the possibility of designing anti-cancer drugs that target these genes.

Overcoming the resistance to current cancer therapies

Steroids, such as dexamethasone, are currently used with other drugs to treat patients with leukaemia and lymphoma. Although resistance to steroids is common, the underlying mechanisms have so far been poorly understood.

Dexamethasone works in part through the control of important messengers in the cells communication network, known as sphingolipid enzymes, which play a role in instructing the cell to live or die.

Interestingly, in the new study led by Prof Neil and Dr Anna Kilbey, which was funded by Bloodwise and Cancer Research UK, researchers found an over activity of RUNX in lymphoma cells interfered with sphingolipids, and caused cells to become resistant to dexamethasone. These results suggest that drugs that can switch off RUNX may be able to reverse steroid resistance in patients.

Samples of DNA. Credit: Wellcome.

Prof Neil says: “The possibility of making existing therapies more active and specific by combining with drugs that inhibit RUNX is a new and exciting prospect. Our collaborators in the US have recently developed drugs that inhibit RUNX, and we plan to test these with existing therapies in blood cancers where MYC and RUNX are both implicated, including multiple myeloma and Burkitt lymphoma.”

Researchers are now gaining a detailed picture on how exactly the RUNX genes enable cancer to develop. Although this is early work, these recent findings shed light on how we could tackle treatment resistance to steroids.

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