Mac lab finds tie between gut and pre-leukemia

A link between signals from the microbiota in the gut and leukemia has been discovered in a collaborative study between a McMaster University lab run by associate professor of medicine Elena Verdú and led by the University of Chicago.

The study published in the journal Nature found a “leaky gut”, that allows movement of microbes usually happy in the small intestine to tissues beyond the gut, in mice with a common genetic mutation associated with leukemia.

More than 15 per cent of people over 60 develop TET2 (tet methylcytosine dioxgenase 2) mutations in blood stem cells. These mutations are passed along to the progeny of the mutated cell during cell division and put these patients at risk for blood cancers. However, only a portion of individuals with this mutation — or mice that lack TET2 — progress to a pre-leukemic state, which suggests an impact by environmental factors.

The study found increased IL-6, a molecule that promotes inflammation and that is released following systemic bacterial dissemination, was critical for the development of the pre-leukemic state in TET2 deficient mice. However, antibiotic treatment aborted the pre-leukemic changes.

An important step was therefore to test mice with this mutation but generated and bred in germ-free conditions at McMaster’s axenic gnotobiotic laboratory, led by Verdú.

“Interestingly, once the TET2 deficient mice were bred at the axenic gnotobiotic laboratory, no changes in IL-6 were observed, and the pre-leukemic state failed to develop”, said Heather Galipeau, a research associate in Verdu’s lab.

Verdú added: “Maintaining intestinal barrier function could be critical for preventing a pre-leukemic state in genetically susceptible people, in order to restrict intestinal microbes to the gut.

“The study opens the way to potential new strategies aimed at strengthening the intestinal barrier or preventing systemic infections to reduce the progression to leukemia in individuals that have a genetic predisposition.”