Human leukaemic stem cells: a novel target of therapy.
Acute myeloid leukaemia (AML) is a life-threatening haematopoietic disease that is characterized by clonal growth and the accumulation of myelopoietic progenitor cells. Although AML cells only have a limited potential to undergo differentiation and maturation, each AML clone is organized in a hierarchical manner similar to normal haematopoiesis. Recent data have shown that each AML clone consists of leukaemic stem cells and their progeny, and that AML stem cells differ from more mature cells in several aspects, including survival and target antigen profiles. Most importantly, AML stem cells, but not their progeny, have the capacity to repopulate haematopoietic tissues with leukaemias in NOD/SCID mice. Furthermore, AML stem cells are thought to be responsible for the infinite growth of leukaemias in patients with AML. The phenotypic properties of AML stem cells have also been described. In most cases, these cells are detectable within the CD34+, CD38-, Lin-, CD123+ subpopulation of AML cells. Because of their AML-initiating and -renewing capacity and their unique phenotype, which includes several molecular targets of drug therapy, AML stem cells have recently been proposed as novel important target cell populations in the context of curative therapies. The present article gives an overview of our knowledge about AML stem cells, their phenotype, and their role as a 'therapy-target' in new concepts to treat and to cure patients with AML.
Department of Internal Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, Austria. wolfgang.r.sperr@univie.ac.at
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Sperr
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Hauswirth
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Florian
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Ohler
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Geissler
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Valent
D005544:Forecasting; D018390:Gene Targeting / Q000379:methods; D015316:Genetic Therapy / Q000379:methods*; D006412:Hematopoietic Stem Cells; D006801:Humans; D007951:Leukemia, Myeloid / Q000473:pathology / Q000628:therapy*; D014411:Neoplastic Stem Cells; D010641:Phenotype