During her prestigious John Goldman Fellowship funded by Leukaemia UK, Dr Mariani and her team at the University of Edinburgh, investigated whether leukaemia-associated macrophages (specialised immune cells) play a role in the development and progression of infant leukaemia. Using advanced mouse models, her research aimed to uncover how these macrophages contribute to the disease, providing critical insights into potential treatment strategies tailored for this vulnerable group of patients. This fascinating approach to treating infant leukaemia also made Dr Mariani the recipient of the 2021 Olive Boles Innovation Award.

The challenge

As part of her Follow-up Fund research project, Dr Mariani is now focusing on acute myeloid leukaemia (AML), a highly aggressive and often treatment-resistant form of blood cancer. Approximately 3,100 people are diagnosed with AML each year in the UK, and with a 5-year survival rate of just 22%, it remains one of the most challenging cancers to treat.

Dr Mariani’s research is centred on two key proteins, GPR56 and GPR97, which are found to be excessively produced in difficult-to-treat AML cases. GPR56 is linked to poor outcomes in AML patients, and recent studies suggest that GPR97 may help make up for when GPR56 has been used up, potentially contributing to treatment resistance. Certain types of leukaemia cells which also produce higher levels of GPR56 are linked to high relapse rates after transplant—an ongoing challenge for these AML patients.

The science behind the research

Dr Mariani’s team is using advanced gene-editing (CRISPR/Cas9) to study how two proteins, GPR56 and GPR97, contribute to AML. They have modified human stem cells to produce a constantly active form of GPR56. Early results show that too much GPR56 makes leukaemia cells grow faster and enables them to resist and survive treatments.

Their research also found that GPR56 helps cells survive chemotherapy and radiation, which may explain why some AML treatments fail. They are now testing GPR97 to see if it plays a similar role. Understanding these proteins could lead to new, more effective treatments for AML.

What does this mean for patients?

The ultimate goal of this research is to develop treatments that can overcome resistance in AML patients by targeting GPR56, GPR97, or their associated pathways. This work could lead to the development of safer, more effective therapies, improving survival rates and quality of life for patients with aggressive AML.

Furthermore, the knowledge gained about GPR56 and GPR97 will contribute to broader scientific understanding, potentially benefiting other areas of cancer research, neurobiology, and blood cell formation. By identifying the precise mechanisms by which these proteins contribute to leukaemia progression and therapy resistance, Dr Mariani’s work holds promise for translating these insights into innovative treatment strategies that could significantly impact the future of AML therapy.