Epigenetic silencing of critical genes through aberrant methylation appears to play a key role in tumor development. To advance our basic understanding of the epigenetic regulation of gene expression in cancer cells, and clinically test the hypothesis that remethylation of genes has therapeutic potential, we will investigate chronic lymphocytic leukemia (CLL) as a model in the projects presented in this program project proposal. However, the ability to meaningfully conduct basic studies and translate important findings to the clinical setting is greatly facilitated by the availability of an extensive repository of tissue samples, with accompanying pathologic and clinical data, procured from relevant patients CLL. This Core, the Pathology/Tissue Procurement Core, through the collaboration of the OSU Leukemia Tissue Bank (LTB), will serve this function in supporting the basic and clinical projects of this Program Project. The OSU leukemia tissue bank has a well-established infrastructure directly under our leadership. The Core will participate in the procurement of procurement of CLL cells and the molecular characterization of CLL cases for the Projects. All the essentials of effective tissue bank management, including the activities of tissue collection, quality control of specimens, tissue storage, procurement of initial and follow-up samples and their pathology and clinical information, data entry and database management, and patient consent and confidentiality are very well developed in this Core. In addition, this Core has the established capacity to process procured specimens for the preparation of pure cell populations (e.g., CLL cells though CD19 positive selection), cell lysates, nucleic acids and proteins in a uniform manner for ready distribution to investigators. Furthermore, the procedures for prioritizing and distributing tissue to a large base of investigators, within and outside our institution, are effectively in place. Against this background, we believe that this Core will function well in the support of the 5 projects proposed in this application, as well as future projects and collaborations. While funding currently exists for the infrastructure of OSU LTB, it is emphasized that there is no overlap in funding requested for this Core, as all of the new work proposed in this Program Project is not currently funded by NCI or other peer reviewed grants.
The Specific Aims of this Core are, therefore, to: 1) provide central collection, processing and a state-of-the-art repository for samples collected from CLL patients treated at OSU, including protocols relevant to this Program Project;2) provide materials from processed CLL samples for the support of Projects 1-5 of this Program Project proposal in a standardized manner, and 3) perform molecular characterization, including cytogenetic fluorescent in-situ hybridization (FISH) studies, lgVH and p53 mutational status, on all CLL cases used in the Projects to permit subsequent correlation with clinical and laboratory results.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA101956-05
Application #
8117631
Study Section
Subcommittee G - Education (NCI)
Project Start
Project End
Budget Start
2010-08-01
Budget End
2011-07-31
Support Year
5
Fiscal Year
2010
Total Cost
$337,691
Indirect Cost
Name
Ohio State University
Department
Type
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
Byrd, John C; Furman, Richard R; Coutre, Steven E et al. (2015) Three-year follow-up of treatment-naïve and previously treated patients with CLL and SLL receiving single-agent ibrutinib. Blood 125:2497-506
Lucas, David M; Ruppert, Amy S; Lozanski, Gerard et al. (2015) Cytogenetic prioritization with inclusion of molecular markers predicts outcome in previously untreated patients with chronic lymphocytic leukemia treated with fludarabine or fludarabine plus cyclophosphamide: a long-term follow-up study of the US intergr Leuk Lymphoma 56:3031-7
Blachly, James S; Ruppert, Amy S; Zhao, Weiqiang et al. (2015) Immunoglobulin transcript sequence and somatic hypermutation computation from unselected RNA-seq reads in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A 112:4322-7
Flynn, J; Jones, J; Johnson, A J et al. (2015) Dinaciclib is a novel cyclin-dependent kinase inhibitor with significant clinical activity in relapsed and refractory chronic lymphocytic leukemia. Leukemia 29:1524-9
Motiwala, T; Kutay, H; Zanesi, N et al. (2015) PTPROt-mediated regulation of p53/Foxm1 suppresses leukemic phenotype in a CLL mouse model. Leukemia 29:1350-9
Claus, Rainer; Lucas, David M; Ruppert, Amy S et al. (2014) Validation of ZAP-70 methylation and its relative significance in predicting outcome in chronic lymphocytic leukemia. Blood 124:42-8
Dong, Shuai; Guinn, Daphne; Dubovsky, Jason A et al. (2014) IPI-145 antagonizes intrinsic and extrinsic survival signals in chronic lymphocytic leukemia cells. Blood 124:3583-6
Kohrt, Holbrook E; Sagiv-Barfi, Idit; Rafiq, Sarwish et al. (2014) Ibrutinib antagonizes rituximab-dependent NK cell-mediated cytotoxicity. Blood 123:1957-60
Wei, Quan-Xiang; Claus, Rainer; Hielscher, Thomas et al. (2013) Germline allele-specific expression of DAPK1 in chronic lymphocytic leukemia. PLoS One 8:e55261
Singh, Rajbir; Mortazavi, Amir; Telu, Kelly H et al. (2013) Increasing the complexity of chromatin: functionally distinct roles for replication-dependent histone H2A isoforms in cell proliferation and carcinogenesis. Nucleic Acids Res 41:9284-95

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