Issues

Fundamental to understanding leukemia pathogenesis and relapse is the concept of the leukemia stem cell (LSC) as the leukemia-initiating cell at the top of the differentiation hierarchy. Papapetrou and colleagues extend this concept to not one but many LSCs sequentially contributing to the disease. The authors develop a framework of LSC generation and evolution through three dimensions: developmental ontogeny, genetic lesions, and differentiation hierarchy. Studying myeloid transformation through these three dimensions across time is essential to understanding its pathogenesis and heterogeneity. For more information, see the article on page 94.