”Identifying Anti-Inflammatory Therapeutics That Prevent Clonal Hematopoiesis Progression in Humans”

As we age, our blood cells develop mutations, most of which are harmless. But sometimes, a mutation gives one blood cell an advantage over others, resulting in clonal hematopoiesis (CH). More than 10% of individuals over 70 have CH, and a small subset of these people develop blood cancer. Unfortunately we do not have treatments to stop people with CH from developing blood cancer yet.

One avenue of research we can explore on the road to finding cancer prevention treatments could be in those born with a RUNX1 gene mutation. RUNX1-FPD patients develop CH at an earlier age and at a much higher rate than the general population. Emerging data across several studies suggest that RUNX1-FPD patients have elevated levels of inflammation as compared to the general population. Could this be part of the reason why patients are at increased risk of cancer? 

Using the power of human genetics tools, Dr. Bick’s project will directly test whether blocking inflammation can lead to less CH. He will do this by using very large population-based genomic sequencing databases to identify whether people who are born with mutations that reduce overall inflammation have less CH. These findings would hone in on which inflammation pathways are the most relevant to target using drugs.

Second, Dr. Bick will query another large database with clinical data and blood samples available 10 years back (total of 300,000 individuals) to identify individuals from the general population who have CH and who started on an anti-inflammatory drug for diseases like rheumatoid arthritis or crohn’s disease. Using these individuals and their blood samples, Dr. Bick will use genetic sequencing to uncover whether the anti-inflammatory drug an individual started taking impacted CH. In other words, could the anti-inflammatory drug reduce the number of hematologic malignancies overall or could it slow the outgrowth of the blood cancer precursor cells over time as compared to individuals with CH not on an anti-inflammatory drug.

If Dr. Bick identifies that a specific class of drugs directly impacts CH, this would be a major advance for all those with CH including RUNX1-FPD patients and would provide the necessary rationale for a future cancer prevention clinical study.