Although we have gained detailed understanding of the intrinsic genetic features of chronic lymphocytic leukemia (CLL) in relation to tumor evolution, we still need to understand the intrinsic genetic features of CLL that impact the CLL cells’s interactions with non-tumor cells within the microenvironment, and reciprocally, how the microenvironment shapes the state of these CLL cells.  We now hypothesize that the state of leukemia cells and their interacting non-CLL immune cells evolve throughout the individual patient’s disease course. 

By leveraging our advanced analytic workflows for genomic analysis and the rich bio-sample repository and infrastructure of the CRC Tissue Core and access to samples collected in the context of clinical trials (Cores 2-3), we plan to complete an immunogenomic analysis of CLL-host immune cell co-evolution.

We will especially focus on studies comparing patient samples with CLL B cells that express high ROR1 vs low  ROR1, since it has been shown by CRC investigators that this accessory signaling pathway has high prognostic significance in CLL. We would like to will integrate these data with information on novel mRNA species (with Project 1), on the functional changes in the tumor (with Project 3) and with antigen presenting cell-T cell interactions (with Project 4).