Awakening dormant haematopoietic stem cells.
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.
Trumpp
Andreas
A
Heidelberg Institute for Stem Cell Technology and Experimental Medicine, German Cancer Research Center, Germany. a.trumpp@dkfz.de
Essers
Marieke
M
Wilson
Anne
A
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
D001152:Arsenicals; D016898:Interferon-alpha; D010087:Oxides; D016179:Granulocyte Colony-Stimulating Factor; D000077237:Arsenic Trioxide