Kelly Bolton, M.D., Ph.D.
2019 Funding recipient
The Impact of Oncologic Therapy on Clonal Hematopoiesis and Therapy-Related MDS
EvansMDS Young Investigator Award
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.
Kelly L Bolton, Ryan N Ptashkin, Teng Gao, Lior Braunstein, Sean M Devlin, Daniel Kelly, Minal Patel, Antonin Berthon, Aijazuddin Syed, Mariko Yabe, Catherine C. Coombs, Nicole M. Caltabellotta, Mike Walsh, Kenneth Offit, Zsofia Stadler, Diana Mandelker, Jessica Schulman, Akshar Patel, John Philip, Elsa Bernard, Gunes Gundem, Juan E Arango, Max Levine, Juan S Medina, Noushin Farnoud, Dominik Glodzik, Sonya Li, Marc E Robson, Choonsik Lee, Paul D P Pharoah, Konrad Stopsack, Barbara Spitzer, Simon Mantha, James Fagin, Laura Boucai, Christopher J Gibson, Benjamin L Ebert, Andrew Young, Todd Druley, Koichi Takahasi, Nancy Gillis, Markus Ball, Eric Padron, David M Hyman, Jose Baselga, Larry Norton, Stuart Gardos, Virginia M Klimek, Howard Scher, Dean Bajorin, Eder Paraiso, Ryma Benayed, Maria E Arcila, Marc Ladanyi, David B Solit, Michael F Berger, Martin Tallman, Montserrat Garcia-Closas, Nilanjan Chatterjee, Luis A Diaz Jr., Ross L Levine, Lindsay M Morton, Ahmet Zehir, Elli Papaemmanuil, Oncologic therapy shapes the fitness landscape of clonal hematopoiesis, Nature Genetics 2020, DOI: 10.1101/848739.