Gut microbiome in ageing - is it the answer to leukaemia progression

Acute myeloid leukaemia (AML) is a highly lethal disease in which the overall survival rate for over 75-year olds has not improved over the last 25-years (1, 2). AML is primarily a disease of the elderly, with three quarters of patients diagnosed after the age of 60 and presently the majority (75%) of these patients die within a year of diagnosis (2).

Moreover, AML alone accounted for 85,000 deaths globally in 2016 and it is estimated this will double by 2040 (3). Understanding the mechanisms involved in the transformation of pre-malignant clones to the AML is key to the prevention of cancer. Presently no intervention during ageing is established to prevent AML progression.

The first step in the development of AML is the foundation of a clone of pre-leukemic cells by the acquisition of "founder" mutations in haematopoietic stem cells. Progression to AML relies on the ability of founder mutations to generate mutant clones. Identification of founder mutations in the blood of the majority of healthy elderly individuals has been shown in a process known Clonal haematopoiesis of Indeterminant Potential (CHIP) (4).

CHIP is present in >90% of individuals above 70-years old, however only very few people in the population suffer from AML (100-150 per 100,000 of the population above 70-years old) (5). Given that only a small fraction of individuals who harbor putative founder mutations go on to develop AML, extrinsic non-cell autonomous factors may be critical factors in disease development.

It is well established that ageing changes the gut microbiota (6) and increasing evidence shows that gut microbiome plays a key role in the development of age related disease. The lab has recently established an in vivo model in the disease modelling unit (DMU) which develops spontaneous AML with ageing. Together with the access to human samples from AML patients the aim of this study is to determine the role of ageing induced changes in gut microbiota on driving/influencing the progression AML.