Preleukemic stem cells: leave it or not?

Acute myeloid leukemia (AML) has been shown to undergo multiple acquired mutations in hematopoietic cell lineages over years before becoming clinically apparent. The early stage of AML (before it becomes clinically recognizable) may be characterized by acquisition of some, but not all, leukemia-related somatic mutations in hematopoietic stem cells (HSCs). The physiological roles of these mutations remain puzzling. These HSCs have been termed as preleukemic HSCs. However, those frequent acquired somatic mutations are also found in healthy aging adults, namely, “age-related clonal hematopoiesis.” Multiple studies have demonstrated that the preleukemic HSCs survive through chemotherapy and then contribute to the relapse and the development of de novo AML. Whether preleukemic HSCs should be targeted or whether a preventive therapy should be considered for those individuals remains to be determined. This article aims to shed light on this special subject and to discuss the roles of preleukemic HSCs in leukemogenesis.