Abstract Pathology/Biospecimen/Biorepository Core (PBC) The PBC will manage the collection of patient-derived biospecimens from blood, bone marrow and tissue (cancer and normal) as determined by the trial parameters often with collections occurring at pre and post treatment time points to meet the research aims of the proposed SPORE projects. The PBC Core will provide collection materials, specimen labels and manage shipments of biospecimens to VAI. The specimen derivatives will be distributed to the locations for assay performance site including the SPORE’s Genomics Core and other collaborating project investigators. Pathology-based histology assessment, DNA methylation EPIC BeadChip arrays and immunophenotype monitoring will be provided by the PBC Core. The PBC Core will assess and maintain excellent quality in the collection of biospecimens for use in the correlative science research that are used to determine efficacy, biological function and mechanistic details for the evaluation of the therapeutic treatments and scientific goals of the SPORE projects. For Project 1, the Core will collect process and store peripheral blood and bone marrow samples related to a randomized study of MC180295+Atezolizumab, MC180295+DAC and MC180295+DAC+Atezolizumab in relapsed or refractory AML/MDS. Biospecimens collected will be managed by the PBC Core with nucleic acids being sent to the Genomics Core for assessment of epigenetic parameters. Immune cell parameters (cell numbers, gene expression in T-cells, T-cell exhaustion parameters) will be measured in the PBC Flow Cytometry Core. Approximately 600 data points will be assayed from this cohort. For Project 2, the Core will collect samples from the clinical trial of combined DNMT and EZH1/2 inhibition that is planned to begin in year 2 with collection and management of peripheral blood and tumor biopsies pre and post therapy to assess epigenetic modulation and biomarkers (done in the Genomics Core) and Immune biomarkers (done in the PBC Core). Approximately 1,400 data points are expected from this cohort. Project 3 will use the PBC Core resources to collect and manage pre and post therapy biospecimens and to provide specimen DNA and RNA derivatives to the Genomic Core for BRCAness gene expression, DNA methylation and global gene expression including ERVs. The PBC Core’s access to the VAI Flow Cytometry Core will provide immune monitoring and the PBC Core’s access to the VAI Genomics Core will provide the Methylation EPIC BeadChip array for evaluation. Approximately 640 to 800 specimens will be tested to meet the aims of this project. The Pathology and Biospecimen Core will provide access and distribution of project specimens to downstream assay sites, whether they are within the Core Technologies at VAI, the Genomics Core at Coriell, principal investigators laboratories or other approve investigators beyond the principal SPORE investigators.