PROJECT SUMMARY

As we age, our blood cells develop mutations. Most mutations are harmless. But sometimes, a mutation gives one blood cell an advantage over others. The mutant cell then expand causing “clonal hematopoiesis.”

More than 10% of individuals over 70 have clonal hematopoiesis. A small number of these people develop blood cancer. We do not have treatments to stop people with clonal hematopoiesis from developing blood cancer.

One clue to stopping blood cancer, comes from people who are born with a mutation in the RUNX1 gene. These patients get clonal hematopoiesis at an early age. They also develop blood cancer at a much higher rate than others. Mice with the RUNX1 mutation have increased inflammation. Blocking inflammation in mice slows clonal expansion and prevents blood cancer. But this theory has not been tested in humans.

Our project directly tests whether blocking inflammation in humans stops clonal expansion and prevents blood cancer. First, we will study people who are born with mutations that lead to less inflammation and test whether they have less clonal expansion and less blood cancer. If this is true, then medications that decreasing inflammation may be a treatment for patients with clonal hematopoiesis.

Second, we will study of 300,000 patients who had blood drawn ten years ago. We will find several hundred patients with clonal hematopoiesis who were started on an anti-inflammatory medicine. We will obtain a second blood sample to measure how their blood clone has grown over time. If blocking inflammation stops clonal growth, we expect that people on antiinflammatory medicine will have slower clonal growth.

If this project is successful, it will show in humans that less inflammation slows clonal growth and stops blood cancer. It may also show which medication or inflammation pathway works best. These observations would spur a randomized human clinical trial using one of these already FDA approved drugs. If successful, the anti-inflammatory medication would be a first treatment for stopping blood cancer in patients with RUNX1 mutations.