PROJECT SUMMARY

In my EvansMDS Young Investigator award I proposed to study how somatic mutations in the blood (clonal hematopoiesis) are impacted by cancer therapy. in some individuals, clonal hematopoiesis will lead to myeloid disease, especially MDS. We previously showed that cancer patients who received therapy have higher frequencies of clonal hematopoiesis. Understanding how oncologic therapy promotes clonal hematopoiesis will provide insight into how oncologic therapy causes MDS. I proposed to perform a large-scale study in 25,000 cancer patients to understand what types of oncologic therapies lead to clonal hematopoiesis. I have completed this aim and the resultant manuscript has been accepted at Nature Genetics. I also proposed to study how clonal hematopoiesis evolves in patients receiving therapies strongly linked to MDS. I have completed sample collection in subjects receiving platinum, topoisomerase II inhibitors and PARPi. I am piloting a custom CH panel with Archer and we plan on completing sequencing of the full sample set in January 2021. Finally, I proposed to define the genetic features of CH that put solid tumor patients at high risk of therapy-related MDS. This is in the final stages of sample acquisition.