The end of the beginning: Application of single cell sequencing to chronic lymphocytic leukemia (CLL).

Single cell analysis has emerged over the past decade as a transformative technology informative for the systematic analysis of complex cell populations such as in cancers and the tumor immune microenvironment. The methodologic and analytical advancements in this realm have rapidly evolved, scaling from but a few cells at its outset to the current capabilities of processing and analyzing hundreds of thousands of individual cells at a time. The types of profiling attainable at individual cell resolution now range from genetic and transcriptomic characterization and extend to epigenomic and spatial analysis. Additionally, the increasing ability to achieve multi-omic integration of these data layers now yield ever richer insights into diverse molecular disease subtypes and the patterns of cellular circuitry on a per-cancer basis. Over the years, chronic lymphocytic leukemia (CLL) has been consistently at the forefront of genomic investigation, given the ready accessibility of pure leukemia cells and immune cells from circulating blood of patients with this disease. Herein, we review the recent forays into the application of single cell analysis to CLL, which are already revealing new understanding of the natural progression of CLL, the impact of novel therapies, and the interactions with co-evolving non-malignant immune cell populations. As we emerge from the 'end of the beginning' of this technologic revolution, CLL stands poised to reap the benefits of single cell analysis from the standpoints of uncovering fresh fundamental biology, and of providing a path to devising regimes of personalized diagnosis, treatment, and monitoring.