title: Awakening dormant haematopoietic stem cells.
abstract: Haematopoietic stem cells (HSCs) in mouse bone marrow are located in specialized niches as single cells. During homeostasis, signals from this environment keep some HSCs dormant, which preserves long-term self-renewal potential, while other HSCs actively self renew to maintain haematopoiesis. In response to haematopoietic stress, dormant HSCs become activated and rapidly replenish the haematopoietic system. Interestingly, three factors - granulocyte colony-stimulating factor, interferon-alpha and arsenic trioxide - have been shown to efficiently activate dormant stem cells and thereby could break their resistance to anti-proliferative chemotherapeutics. Thus, we propose that two-step strategies could target resistant leukaemic stem cells by priming tumours with activators of dormancy followed by chemotherapy or targeted therapies.
authors.affiliation: Heidelberg Institute for Stem Cell Technology and Experimental Medicine, German Cancer Research Center, Germany. a.trumpp@dkfz.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Trumpp
authors.forename: Marieke
authors.initials: M
authors.lastname: Essers
authors.forename: Anne
authors.initials: A
authors.lastname: Wilson
mesh_terms: D000818:Animals; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000276:immunology / Q000494:pharmacology*; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology*; D048708:Cell Growth Processes / Q000187:drug effects / Q000276:immunology; D016179:Granulocyte Colony-Stimulating Factor / Q000276:immunology / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology / Q000494:pharmacology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D010087:Oxides / Q000276:immunology / Q000494:pharmacology*; D055153:Stem Cell Niche / Q000276:immunology
chemical_list: D001152:Arsenicals; D016898:Interferon-alpha; D010087:Oxides; D016179:Granulocyte Colony-Stimulating Factor; D000077237:Arsenic Trioxide