title: The essence of leukemia stem cells.
abstract: The leukemia stem cell (LSC) model has received considerable attention in the past 20 years with the identification of rare cell populations expressing stem cell markers in leukemia cell populations. LSCs are thought to be responsible for leukemia initiation, recurrence, and drug resistance, thus being regarded as excellent targets for developing curative therapies. However, several features of LSCs have recently been challenged. It has become increasingly evident that LSC phenotypes vary among patients. Technical variation of xenograft assays also affects the results, with a trend for more immunodeficient strains allowing the engraftment of variable LSC populations. Studies using mouse leukemia models have shown that not all leukemias are driven by rare and primitive LSCs, instead containing a large population of LSCs expressing mature markers. In addition, recent insights have highlighted genetic variations as important sources of tumor heterogeneity, indicating that the LSC model may not necessarily explain the heterogeneity observed in some leukemias. Nevertheless, several lines of evidence still suggest the existence of primitive LSCs that are associated with therapeutic resistance and poor prognosis in leukemia. This article summarizes current knowledge of LSCs and discusses the challenges ahead.
authors.affiliation: Division of Cellular Therapy, The Institute of Medical Science, The University of Tokyo.
authors.forename: Susumu
authors.initials: S
authors.lastname: Goyama
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D006801:Humans; D007938:Leukemia / Q000378:metabolism / Q000628:therapy; D014411:Neoplastic Stem Cells / Q000378:metabolism; D011230:Precancerous Conditions