Microbiome predicts B-ALL predisposition

Researchers have used mouse models to demonstrate that the gut microbiome profile can function as biomarker to identify predisposed carriers at risk to develop leukaemia. Furthermore, in these models, microbiome deprivation via antibiotic treatment is a risk factor for leukaemia development.

Dr Carolina Vincente-Dueñas (Institute of Biomedical Research of Salamanca, Spain) presented the pre-clinical data [1], in which her lab tested the hypothesis of whether the gut microbiome may serve as an integration hub for environmental signals that modulate the risk of developing B-cell acute lymphoblastic leukaemia (B-ALL), by using a murine model of human B-ALL (Pax5+/- mice).

Pax5+/- mice were raised in either a normal environment or an infection-free environment. The host-gut microbiome of Pax5+/- mice was compared with wildtype mice in both environments. Previous studies have shown that a normal environment increased the incidence of B-ALL in these mice. Furthermore, to determine the contribution of intestinal microbiota to B-ALL development, the gut microbiome was depleted in Pax5+/- and wildtype mice by treating them with an antibiotic cocktail added to their drinking water for a period of 8 weeks. The mice were followed up for 2 years for their gut microbiome and leukaemia development.

The researchers observed that microbiome disturbance by antibiotic treatment early in life was sufficient to induce leukaemia in predisposed mice (48%) even in the absence of an infective environment. In the presence of infectious stimuli, antibiotic treatment increased B-ALL incidence in predisposed mice from 22% to 63%. Microbiome analysis of faecal samples over 2 years found that genetic predisposition to B-ALL associated with a distinct gut microbiome, with a 96.8% prediction rate.

In conclusion, microbiome profiles provide a biomarker that might be used to identify predisposed carriers at risk to develop leukaemia. Furthermore, this study identified microbiome deprivation via antibiotic treatment as a risk factor for leukaemia development. By modulating the microbiome early in life, the risk to develop leukaemia may be reduced in predisposed individuals.

1. 1. Vicente-Dueñas C, et al. An intact gut microbiome protects genetically predisposed mice against leukemia. EHA25 Virtual, 11-21 June 2020, Abstract S100.