PROJECT SUMMARY – LEUKEMIA RESEARCH (LR) The Leukemia Research (LR) Program at The Ohio State University Comprehensive Cancer Center (OSUCCC), led by John C. Byrd, MD, and Ramiro Garzon, MD, has 57 members from 7 Departments and 4 Colleges (Engineering, Pharmacy, Medicine, and Veterinary Medicine). The LR Program remains focused on the etiology, pathogenesis, prognosis, and treatment of leukemia, with emphases on acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), hairy cell leukemia (HCL) and adult T-cell leukemia (ATL). LR has demonstrated unique strengths in its ability to translate preclinical findings to clinical testing, and ultimately to clinical application. Given the breadth of basic, preclinical, translational and clinical, within the LR Program, we will focus on the following two specific aims: 1) To Explore and integrate genetic, epigenetic, non-coding RNAs, and immunosuppressive features of leukemic cells in order to enhance risk stratification and target identification; 2) To foster preclinical and clinical development of epigenetic, targeted, and immunologic therapeutics directed at the causes of leukemic transformation, its progression and ultimate focus on curing these diseases. LR Program members published 702 cancer-relevant manuscripts between 12/01/14 and 11/30/19. Of these, 33% were intra- programmatic (multiple authors from LR Program), 23% were inter-programmatic (authors from multiple OSUCCC Programs), and 77% were multi-institutional (authors from both LR and another institution). The total collaborative publications is 88%. LR Program funding stands at $11.7M in overall direct, cancer-focused funding, of which $6.3M is peer-reviewed, including $5.1M direct funding from NIH ($4.9M from NCI). Over the last 5 years, LR Program members have accrued 8,835 participants to trials; 1,582 to interventional trials (including 1,556 therapeutic trials) and 7,253 to non-interventional trials. Future plans include: 1) enhancement of collaborative science to further improve the quality of our discovery and translational work; 2) further dissection of the genetic subtypes of leukemia to potentially re-define how AML and CLL are classified and treated using precision medicine-based approaches; 3) integration of patient-friendly, targeted and immune therapies to develop curative treatment approaches; and 4) focused recruiting of mid-level funded investigators with dedicated research areas that complement the LR Program and also the Pelotonia Institute for Immuno- Oncology. Overall, our program is committed to support the development of a chemotherapy-free approach to treat leukemia. Therefore, this strategy will be prioritized over conventional chemotherapy approaches through early investigator initiated trials along with the BEAT AML and the Alliance consortia. Through a similar path, an MDS trial (Stop MDS™) will be been initiated and will focus on an area of unmet need. Last, our program will ...