More than half of people with familial platelet disorder (FPD) are at risk of developing the blood cancer acute myeloid leukemia (AML). Individuals with FPD are born with mutations in a gene called RUNX1 and their cells may develop additional mutations over time that can trigger the development of AML. By performing genetic sequencing, we identified 16 patients with AML who have inherited RUNX1 mutations as well as additional mutations in known cancer-causing genes.
We propose to study 1) how RUNX1 mutations create a "pre-leukemic" environment, 2) which inflammation-causing cytokines present in this "pre-leukemic" environment and 3) which of these cytokines then contributes to disease progression and to full-blown leukemia. We also found that samples from the 16 patients were sensitive to certain drugs, so we will use this information to help identify new treatment strategies for these patients. The knowledge gained in this study will help determine effective treatments to prevent FPD from transforming to AML, leading to improved outcomes for patients with FPD. In the long term, we hope to use the information gained from our study to discover how to predict which people with FPD will develop AML and how best to monitor families with the RUNX1 mutation for early detection of AML, as well as expanding our database of FPD patients and families. This will also allow us to design clinical trials aimed at early intervention in these patients and their family members who carry inherited RUNX1 mutations.