Prof. Deb White: Precision Medicine and the gut microbiome in ALL
Acute lymphoblastic leukaemia (ALL) is the most common childhood cancer and remains the leading cause of non-traumatic death in children. For adolescents and young adults with ALL the therapeutic outcomes are poor. Most older adults will die of their disease. ALL is characterised by recurrent gene fusions and associated structural chromosomal abnormalities. New technologies, like Next Generation Sequencing (NGS), are now providing us with a wealth of genomic information. Applying these techniques in ALL has identified new DNA mutations in patients with ALL known to confer high-risk, however it is also identifying new subgroups and recurrent gene fusions for which biological and clinical implications remain unclear.
Professor White is the head of the Australian Centre for ALL Genomics and this project is looking to introducing a more personalised approach to care for patients with ALL by incorporating the genomic information gained through NGS into clinical care, using this genomic information to help systematically identify druggable targets and effective rational therapies. The Leukaemia Foundation’s support to this project will make NGS testing available to an additional 100 newly diagnosed patients Australia wide.
In addition to providing NGS sequencing, Prof White’s team will also investigate ALL disease invasion and penetration into the central nervous system. Create a model to investigate cooperating mutations (ie when two or more genes are often seen mutated together in ALL). Perform high throughput drug screening in order to test the sensitivity of ALL to a panel of drug agents.
There is now clear evidence that the gut microbiome plays an unexpectedly critical role in modulating responses to chemotherapy and immunotherapy in other cancers, however the relationship between gut microbiome and treatment responses and survival in ALL, is relatively unexplored. Preliminary results from Prof Whites lab have shown for the first time that the gut microbiome can impact the immune response in ALL. This is a globally significant study as it is the first to identify a relationship between gut microbiome and immune response.
This project seeks to ask does the composition of a patient’s microbiome help to determine how they respond to treatment and, if the composition of the microbiome is changed, does the patients respond and recover better?
This project is kindly supported through the Estates of Edward Rhoades, Florence Brown and Phil’s Dive for a Cure.