“Modeling RUNX1-FPD to Identify Interventions Suppressing Myeloid Expansion and Clonal Evolution”

RUNX1-FPD is associated with life-long bleeding and bruising, and a high risk of developing blood cancers, most commonly myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).

Before progressing to overt leukemia, patients with a RUNX1 mutation develop clonal hematopoiesis (CH) more frequently and earlier than the healthy population. CH occurs when a single blood stem cell with a second mutation in a cancer-associated gene starts to crowd out other healthy blood stem cells by dividing and passing on the second mutation to its daughter cells. 

How this stem cell with a second mutation is able to crowd out healthy cells in RUNX1-FPD individuals is not well understood. Over the last few years, several studies have identified inflammation as a possible culprit in nurturing these mutated stem cells at the expense of the stem cells without a second mutation. 

Dr. Agarwal is one of the investigators in the field who has been hot on the inflammation trail in RUNX1-FPD. In this project, she will be studying which pro-inflammatory pathways from patient bone marrow samples create the conditions that could be nurturing these mutated stem cells, which are the precursors to blood cancer. Once Dr. Agarwal hones in on the most harmful inflammatory pathway(s), her group will conduct lab tests using FDA-approved drugs that block those identified pathways and thereby  prevent blood cancer precursor stem cells from crowding out the healthy, unmutated blood cells.