Epigenetic silencing of critical genes through aberrant methylation appears to play a key role in tumordevelopment. To advance our basic understanding of the epigenetic regulation of gene expression in cancercells, and clinically test the hypothesis that remethylation of genes has therapeutic potential, we willinvestigate chronic lymphocytic leukemia (CLL) as a model in the projects presented in this program projectproposal. However, the ability to meaningfully conduct basic studies and translate important findings to theclinical setting is greatly facilitated by the availability of an extensive repository of tissue samples, withaccompanying pathologic and clinical data, procured from relevant patients CLL. This Core, thePathology/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 leukemiatissue bank has a well-established infrastructure directly under our leadership. The Core will participate in theprocurement of procurement of CLL cells and the molecular characterization of CLL cases for the Projects. Allthe essentials of effective tissue bank management, including the activities of tissue collection, quality controlof specimens, tissue storage, procurement of initial and follow-up samples and their pathology and clinicalinformation, data entry and database management, and patient consent and confidentiality are very welldeveloped in this Core. In addition, this Core has the established capacity to process procured specimens forthe preparation of pure cell populations (e.g., CLL cells though CD19 positive selection), cell lysates, nucleicacids and proteins in a uniform manner for ready distribution to investigators. Furthermore, the procedures forprioritizing and distributing tissue to a large base of investigators, within and outside our institution, areeffectively in place. Against this background, we believe that this Core will function well in the support of the5 projects proposed in this application, as well as future projects and collaborations. While funding currentlyexists for the infrastructure of OSU LTB, it is emphasized that there is no overlap in funding requested for thisCore, as all of the new work proposed in this Program Project is not currently funded by NCI or other peerreviewed grants.
The Specific Aims of this Core are, therefore, to: 1) provide central collection, processingand a state-of-the-art repository for samples collected from CLL patients treated at OSU, including protocolsrelevant to this Program Project; 2) provide materials from processed CLL samples for the support of Projects1-5 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 allCLL cases used in the Projects to permit subsequent correlation with clinical and laboratory results.
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