SAHMRI blood cancer research expertise on the frontline of battle against chronic myeloid and other leukaemia
SAHMRI (South Australian Health and Medical Research Institute) blood cancer programme became research into acute lymphoblastic leukaemia, acute myeloid leukaemia, chronic myeloid leukaemia, myelodysplastic syndromes and myeloproliferative neoplasms.
Image courtesy South Australian Health and Medical Research Institute
SAHMRI (South Australian Health and Medical Research Institute) built an international reputation for breakthroughs in blood cancer research, with professor Timothy Hughes founding leader of was originally known as its cancer theme.
SAHMRI’s blood cancer programme became research into acute lymphoblastic leukaemia, acute myeloid leukaemia, chronic myeloid leukaemia, myelodysplastic syndromes and myeloproliferative neoplasms.
Chronic myeloid leukaemia was predicted to become the most prevalent leukaemia in Australia within the next 20 years. Only about 25% of patients achieved the best outcome: treatment-free remission. Around 50% still required lifelong treatment and another 25% developed resistance or intolerance to treatment. SAHMRI’s chronic myeloid leukaemia group was trying to improve these outcomes using precision medicine that specified treatment for the patient’s specific needs and disease characteristics.
The chronic myeloid leukaemia group was exploring biomarkers indicating who needed a more intensive approach to therapy from the start and who could be safely managed with standard therapeutics. The group and others showed that carefully selected people with excellent responses to therapy could stop treatment, with around half remaining in remission long-term. This was called treatment-free remission. SAHMRI researchers were at the forefront of global efforts to develop tyrosine kinase inhibitors that reduced chronic myeloid leukaemia from a death sentence to a manageable chronic condition.
Acute lymphoblastic leukaemia was the most common childhood malignancy and the leading causes of non-traumatic death in children. For adolescents and young adults with acute lymphoblastic leukaemia, outcomes were poor. SAHMRI’s acute lymphoblastic leukaemia research group’s primary focus was defining the genomic basis of the disease in adults and children. The significance of this group's work was that timely therapeutic intervention would, in most cases, improve both short- and long-term outcomes for patients.
As the national referral centre for acute lymphoblastic leukaemia genomic screening, SAHMRI’s group used next-generation sequencing to identify cancerous changes in samples from patients at diagnosis and relapse. The clinical relevance of these findings was that many genomic changes were sensitive to already available targeted therapies that had known clinical safety profiles. For genomic alterations where the risk was unknown or a drug target couldn’t be identified, the group made invitro and invivo investigations to assess the potential of the lesions to cause disease and to test drug sensitivity against increasing therapeutic agents.
While acute lymphoblastic leukaemia was a disease of bone marrow and blood cells, other factors likely played a role in the disease, therapeutic response and short- and long-term toxicity. To explore this, with the Lynn EMBL Australia group at SAHMRI, the acute lymphoblastic leukaemia team’s studies expanded to in-depth analyses of the immune system and associated gut microbiota of patients. The importance of these analyses was that many of these factors were modifiable. The researchers also assessed such modifications on clinical response improvement and reduced toxicity in the lab.
The SAHMRI group’s challenge was to incorporate knowledge gained through its analyses into clinical care. To assist this, the team worked with all major clinical and research groups around Australia and with groups specialising in machine learning algorithms to ensure data generated in a form to be applied clinically.