Identification of therapeutic pathways in leukaemia via glucocorticoid-induced changes in DNA methylation

Professor Ian Morison
University of Otago, Dunedin 

What is the problem and who does it affect?

Many childhood cancers are life-threatening, and current treatments are often insufficient to fight off the rapidly multiplying cancerous cells. Conventional chemotherapy still fails in approximately 20 per cent of patients who’ve been diagnosed with acute lymphoblastic leukaemia (ALL).


What is this project hoping to achieve?

Prof Ian Morison and his colleagues have noted epigenetic changes in genes when treated with glucocorticoids, a mainstay in chemotherapy treatment, especially for lymphoid cancers. They aim to better understand these changes, and hope to identify new strategies to target specific pathways to improve treatment.

An issue with glucocorticoids is their ability to promote side-effects associated with their use. These include diabetes, gastric ulcers, weight gain, and mental health changes among others. An understanding of the genomic pathways could be used to abate the presence and mitigate the severity of such side-effects.

By targeting these cultured cell lines with dexamethasone, he and his team can investigate novel pathways through which the therapeutic effects of glucocorticoids are mediated.

A child’s sensitivity to glucocorticoids is a major predictor of prognostic outcomes, and often sensitivity is lessened due to repeat bouts of therapy, which leaves the child even more vulnerable to the cancer.

Greater knowledge in this area could translate to practical application, with the potential to result in better prognoses for young cancer patients.