The Genomic and Epigenomic Landscape of Chronic Lymphocytic Leukemia

Abstract

Due to its prevalence, protracted natural history, and accessibility to suitable material, chronic lymphocytic leukemia (CLL) remains an attractive model to understand the processes of cancer progression and evolution. Genome-wide genomic and epigenetic approaches have delivered an unparalleled view of the architecture of the CLL (epi)genome, so that we now possess an extensive catalogue of the copy number, mutational and epigenetic landscape of the disease, a precise description of clonal evolution, several key molecular mechanisms that drive genomic instability and therapeutic resistance, and an in-depth list of gene loci that contribute to disease predisposition. This work has provided novel insights into the prognostic importance of copy number changes, and identified novel prognostically relevant gene mutations that function within biological pathways that are attractive treatment targets and epigenetic alterations that point to the disease’s cell of origin. Herein, an overview of recent (epi)genomic landmark discoveries is discussed, with associated clinical and biological implications.