The Ohio State University is requesting support for a Specialized Program of Research Excellence (SPORE) in leukemia. The focus and goal of this application is highly translational research that improves our understanding of leukemia development, risk stratification and therapy. Central to the success of this SPORE is a cadre of senior investigators who have worked together for years to identify new prognostic factors and treatments for different types of leukemia. Realizing the value of this group and the potential for a Leukemia SPORE to further enhance translational research outcome, OSU has committed financial resources of over $1.4 million per year to support this effort. This SPORE will work to develop novel prognostic factors and therapies to benefit leukemia patients, and additionally will actively engage women and minorities in this endeavor both at the investigator and patient levels. The Projects in this SPORE are: Project 1 - Drs. de la Chapelle &Byrd: Early Predisposing Genes and Risk Stratification for CLL. This project will examine biology of DAPK1 and the prognostic significance of early events in risk stratification of CLL. Project 2 - Drs. Bloomfield &Marcucci: Molecular Characterization and Risk Stratification of Acute Myeloid Leukemia (AML). This project will study the impact of select prognostic gene (FLT3 ITD, MLL PTD, NPM1, WT-1, CEBPA, KIT) mutations, aberrant gene (BAALC, ERG, FLT3, MN1 and EVI1) expression, and mRNA/miRNA expression profiles, on predicting treatment outcome of newly diagnosed AML patients. Project 3 - Drs. Byrd &Lin: Lenalidomide as an Immune Modulating Agent for Chronic Lymphocytic Leukemia (CLL). This work will focus on the mechanism of lenalidomide-induced CLL cell activation and its contribution both to efficacy and to tumor flare, and will examine strategies to reduce morbidity and improve efficacy. Project 4 - Drs. Caligiuri, Marcucci, &Blum: Pre-Clinical and Clinical Investigation of MLL-PTD AML. This project will focus on utilizing a novel MLL PTD mouse model to characterize events in leukemic transformation and to pre-clinically study novel therapeutic approaches for this subset of patients. This project will also initiate a clinical trial of epigenetic therapy to improve the outcome of patients with MLL PTD[+] AML. Project 5 - Drs. Grever &Lee: Pre-clinical and Clinical Development of Silvestrol in CLL. This project will investigate how the novel agent silvestrol mediates B-cell specific cytotoxicity via translational inhibition of apoptotic proteins crucial to B-cell survival, and will facilitate Phase I development of this agent through the NCI. Five Cores accompany these Projects: (A-SPORE Leukemia Tissue Bank;B-Biostatistics;C-Biomedical Informatics;D-Medicinal Chemistry and;E-Administration and Operations). In addition, we have developed a robust developmental research program and career development program to augment the efforts of this SPORE. We believe that this SPORE group, as a multidisciplinary, highly interactive and accomplished team, will have a substantial impact on improving the clinical outcome of leukemia patients.