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Sample Processing and Analysis Core

$270,948P01FY2017CANIH

Brigham And Women'S Hospital, Boston MA

Investigators

Linked publications, trials & patents

Abstract

The mission of Core B is to facilitate translational and laboratory-based research performed by program investigators in Projects 1-5. The core has 2 functions. The first is to collect and bank primary AML samples, AML cell lines, and AML primary xenografts (primagrafts), for distribution to program investigators for their studies. The second function to perform a set of analyses on all newly diagnosed AML patients and all patients going on clinical trials that include mutation analsysis and BHS priming. The repository functions of the core include the acquisition of appropriate patient samples, isolation and cryopreservation of mononuclear cells, separation and storage of plasma or serum, isolation and storage of genomic DNA, maintenance of a data-base annotating patient samples and distribution of samples to program investigators. While the core will not do in vivo or in vitro drug testing itself, it will provide live and/or cryopreserved primary cells to Projects 1-5 for use in vitro and in vivo preclinical testing of novel therapeutic agents and combinations of therapies as described in each project. For in vivo testing of drugs, most of the projects will utilize AML cell lines expressing luciferase so that the mice can be readily imaged in real time, and the core will generate and store these lines for the use of all projects. Also, the use of primagrafts is of increasing value and interest in the field and the program investigators will have access to a growing panel of these cells for in vivo studies. As noted, these are primary AML cells selected for passage in immunocompromised NSG mice. By using a standard set of banked cell lines and primagrafts, we can minimize variability between labs, and also fully characterize the cell lines and primagrafts by SNP analysis, Profile mutation analysis, and karyotype. Core B does not plan on banking engineered murine leukemia cell lines initially, but if lines become of interest to more than one project, these lines could be added to the bank. The Core will enable all Projects to utilize the models that are most scientifically relevant to their studies, rather than be limited by the internal capabilities and sample access within the individual Project laboratories. Given the criticality of in vivo studies for establishing proof-of-concept and as a bridge to clinical testing, this Core is essential for the translational goals of the Program as a whole.

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