Interdependencies of Intratumoral Genetic Heterogeneity and the Immune Microenvironment in Chronic Lymphocytic Leukemia

The tumor microenvironment (TME) and somatic mutations drive progression of chronic lymphocytic leukemia (CLL). Integrated bulk and single-cell RNA sequencing (RNA-seq) of paired peripheral blood (PB) and lymph node (LN) samples from patients with treatment naïve CLL showed upregulation of oncogenic processes in LN attributable to a minor population of activated tumor cells. A 10-gene activated tumor signature was positively correlated with activated CD4+ T cells and M2 macrophages in the TME. Whole exome sequencing of paired PB and LN samples showed subclonal expansion in LN in some patients. In remaining patients with clonal stability between PB and LN, a T-cell inflamed TME was detected by RNA-seq. These data connect the TME with molecular events in the pathogenesis of CLL. Overall design: Single cell RNA sequencing (scRNA-seq) of paired peripheral blood and lymph node (n = 5 patients).