The role of the GADD45A gene in AML pathogenesis and response to therapy
The Acute Leukaemia Laboratory has a fundamental interest in Acute Myeloid Leukaemia (AML). This devastating disease is the most common form of acute leukaemia in adults and is responsible for one fifth of all childhood leukaemia cases. AML comprises several subtypes, characterised by different combinations of mutations and outcomes to therapy. With the recent advances in genomics-based applications, research in this field has been accelerated and we have been using these sophisticated technologies to better understand the mutations responsible for this disease, and to investigate the use of new targeted therapies to treat AML patients who currently face poor outcomes on standard therapy.
What we aim to achieve
The research carried out by the Acute Leukaemia Laboratory strives to better understand the mechanisms underlying AML, allowing development and testing of new drugs with the ultimate goal of improving treatment outcomes for patients.
What are the next steps and milestones for your research?
Our previous research has shown that a particular tumour suppressor gene, GADD45A, is turned off during development of AML in some patients. We have now shown that this occurs in concert with a set of mutations that are known to occur prior to leukaemia development in the patient, and which convert the healthy cells to a “pre-leukaemic state”. We are now investigating how the GADD45A gene is silenced in this group of AML patients, and how this changes the properties of normal blood cell precursors, such that a high-risk leukaemia develops. This knowledge may pave the way for investigating selected drugs that may be able to reactivate the faulty GADD45A gene in these patients and thus halt the cancer progression.
What motivates you to pursue cancer research?
Acute Myeloid Leukaemia is a a group of diseases and patient response to treatment across these subtypes is highly variable. Overall survival for adults with AML is still only 30-40%, and for some subtypes, prognosis is dismal, with a median overall survival of just 10 months. There is great need to develop new and more selective treatment approaches that will effectively target individual AML subtypes and improve the outcome and lives of patients with this devastating disease.
My message to supporters:
Dissecting and understanding the complex biology underpinning cancer development and progression is a critical step for the development of new, more targeted and effective therapies. None of this important research would be possible without the generous donation of patient samples for research, as well as funding support from the Cancer Council SA.