The permissive immune microenvironment is a critical regulator of disease progression from SMM to overt MM, and defining these alterations is critical for the development of translational prognostic and mechanistic models of disease progression

Description

Novel genomic approaches may enable better prediction of progression risk to multiple myeloma (MM) from the more indolent precursor stages of monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). In support of this, the Ghobrial and Getz laboratories have previously collected, analyzed, and published biomarkers from the tumor cell fraction of SMM patients that efficiently stratified patients in a model of progression to MM, namely the presence of genomic abnormalities involving MYC, TP53, and the RAS genes. During this funding period, we focused on refining tumor-based genomic assays for the early detection and monitoring of MM pathognomonic events in patients with MGUS/SMM. We describe two research activities involving genome sequencing of tumor cells: (1) the development of a novel approach for the isolation and sequencing of rare tumor cells from peripheral blood, for minimally invasive characterization of multiple myeloma disease pathology and (2) the analysis of genomes from bone marrow samples of participants from the precursor crowd (PCROWD) study with MGUS/SMM.