BIOSPECIMENS AND XENOGRAFT

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Abstract The major goals of Core 2 are to provide the SPORE with the infrastructure and professional expertise needed to bank, characterize and distribute primary specimens and patient-derived xenograft (PDX) models. These will be prospectively collected from patients through established protocols developed by the Administrative Core (Core 1), assayed using novel molecular biomarker tests by the Translational Core (Core 3) and serve as essential reagents for each of the Research Projects. Core 2 will be jointly directed by Drs. Jerome Ritz and Dr. David Weinstock. Dr. Jerome Ritz has worked in leukemia and transplant research at DFCI for more than 30 years and has extensive experience in cell collection, processing, cryopreservation, flow cytometric analysis and purification, transplant immunology, and database development. Dr. Ritz is currently the Executive Director of the Connell O'Reilly Cell Manipulation Core Facility (CMCF) at DFCI. The Pasquarello Tissue Bank for Hematologic Malignancies was established as a unit of the CMCF in 2001 and will be responsible for processing, banking and distribution of primary myeloid malignancies for this SPORE. This resource has already acquired over 4,000 bone marrow samples from over 1,500 unique patients with myeloid leukemias that are available for use by SPORE investigators. Dr. Weinstock directs the DFCI Hematologic Malignancy PDX repository, which already contains >300 transplantable PDX models that have been viably cryopreserved and are available for SPORE investigators. These are fully characterized by whole transcriptome sequencing, DNA sequencing, immunophenotyping and other molecular assays. Existing patient samples and PDX lines have already been shared with Project investigators. Moreover, the Core has extensive experience with utilizing primary patient specimens for in vitro assays and PDX models for in vivo pre-clinical trials of novel therapies. Aim 1 of the Core is to acquire primary samples from patients with myeloid malignancies enrolled in clinical research protocols and to isolate and preserve viable mononuclear cells, DNA and plasma. Aim 2 is to establish, characterize, and distribute xenograft models of myeloid malignancies and facilitate pre-clinical trials in collaboration with the Projects. Aim 3 is to maintain annotated databases containing pathologic, cytogenetic and molecular information for clinical samples and xenografts obtained from patients with myeloid malignancies. By successfully pursuing these aims, the Core plays an essential role in the success of the SPORE and its collective efforts to improve the diagnosis and treatment of patients with myeloid neoplasms.