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.

Public Health Relevance

This leukemia SPORE application actively engages in clinical and laboratory translational research of adult leukemia. The findings coming forth from this SPORE are relevant to understanding the pathogenesis, risk stratification, and therapy of leukemia with the ultimate goal of improving clinical outcome for patients.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA140158-03
Application #
8110635
Study Section
Special Emphasis Panel (ZCA1-GRB-I (M1))
Program Officer
Nothwehr, Steven F
Project Start
2009-08-17
Project End
2014-07-31
Budget Start
2011-08-12
Budget End
2012-07-31
Support Year
3
Fiscal Year
2011
Total Cost
$2,185,000
Indirect Cost
Name
Ohio State University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
Mims, Alice S; Mishra, Anjali; Orwick, Shelley et al. (2018) A novel regimen for relapsed/refractory adult acute myeloid leukemia using a KMT2A partial tandem duplication targeted therapy: results of phase 1 study NCI 8485. Haematologica 103:982-987
Walker, Christopher J; Oakes, Christopher C; Genutis, Luke K et al. (2018) Genome-wide association study identifies an acute myeloid leukemia susceptibility locus near BICRA. Leukemia :
Eisfeld, Ann-Kathrin; Kohlschmidt, Jessica; Mrózek, Krzysztof et al. (2018) Mutation patterns identify adult patients with de novo acute myeloid leukemia aged 60 years or older who respond favorably to standard chemotherapy: an analysis of Alliance studies. Leukemia 32:1338-1348
Eisfeld, Ann-Kathrin; Kohlschmidt, Jessica; Mrózek, Krzysztof et al. (2018) NF1 mutations are recurrent in adult acute myeloid leukemia and confer poor outcome. Leukemia 32:2536-2545
Sekeres, Mikkael A; Othus, Megan; List, Alan F et al. (2017) Randomized Phase II Study of Azacitidine Alone or in Combination With Lenalidomide or With Vorinostat in Higher-Risk Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia: North American Intergroup Study SWOG S1117. J Clin Oncol 35:2745-2753
Park, I-K; Blum, W; Baker, S D et al. (2017) E3 ubiquitin ligase Cbl-b activates the p53 pathway by targeting Siva1, a negative regulator of ARF, in FLT3 inhibitor-resistant acute myeloid leukemia. Leukemia 31:502-505
Papaioannou, Dimitrios; Nicolet, Deedra; Volinia, Stefano et al. (2017) Prognostic and biologic significance of long non-coding RNA profiling in younger adults with cytogenetically normal acute myeloid leukemia. Haematologica 102:1391-1400
Eisfeld, Ann-Kathrin; Kohlschmidt, Jessica; Mrózek, Krzysztof et al. (2017) Mutational Landscape and Gene Expression Patterns in Adult Acute Myeloid Leukemias with Monosomy 7 as a Sole Abnormality. Cancer Res 77:207-218
Eisfeld, A-K; Kohlschmidt, J; Schwind, S et al. (2017) Mutations in the CCND1 and CCND2 genes are frequent events in adult patients with t(8;21)(q22;q22) acute myeloid leukemia. Leukemia 31:1278-1285
Walker, C J; Eisfeld, A-K; Genutis, L K et al. (2017) No evidence for microsatellite instability in acute myeloid leukemia. Leukemia 31:1474-1476

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