The Road to Pathogenesis: Charting the Development of LSCs and Pre-LSCs

Leukemia stem cells (LSCs, also known as leukemia-initiating cells) are thought to be responsible for leukemia initiation, maintenance and recurrence. Elimination of LSCs is therefore seen as a potential cure for this fatal disease. LSCs may arise from self-renewing hematopoietic stem cells (HSCs) as well as committed progenitors. The cross-talk between leukemic cells and their niche is already known to contribute to leukemia pathogenesis, and recent studies have further proposed a new model in which a series of transforming events initially gives rise to pre-leukemic stem cells (pre-LSCs) prior to the formation of fully transformed LSCs. This research topic will highlight recent and ongoing advances in our understanding of the cell of origin of leukemia, the role(s) of pre-LSCs in leukemia development, and the aberrations that lead to LSC formation and subsequent pathogenesis. Understanding the causes of leukemic and pre-leukemic mutations, and why these mutations are found in specific cells, is an important step in monitoring the disease as well as delineating its development. We welcome original research and review articles as well as shorter articles such as opinion and perspectives.