The versatile landscape of haematopoiesis: are leukaemia stem cells as versatile?

Since the early 1980s, developing haematopoietic cells have been categorised into three well-defined compartments: multi-potent haematopoietic stem cells (HSC), which are able to self-renew, followed by haematopoietic progenitor cells (HPC), which undergo decision-making and age as they divide rather than self-renew, and the final compartment of functional blood and immune cells. The classic model of haematopoiesis divides cells into two families, myeloid and lymphoid, and dictates a route to a particular cell fate. New discoveries question these long-held principles, including: (i) the identification of lineage-biased cells that self-renew; (ii) a strict myeloid/lymphoid dichotomy is refuted by the existence of progenitors with lymphoid potential and an incomplete set of myeloid potentials; (iii) there are multiple routes to some end cell types; and (iv) thymocyte progenitor cells that have progressed some way along this pathway retain clandestine myeloid options. In essence, the progeny of HSC are more versatile and the process of haematopoiesis is more flexible than previously thought. Here we examine this new way of viewing haematopoiesis and the impact of rewriting an account of haematopoiesis on our understanding of what goes awry in leukaemia.