Targeting leukemic stem cells by breaking their dormancy.
Transient or long-term quiescence, the latter referred to as dormancy are fundamental features of at least some adult stem cells. The status of dormancy is likely a critical mechanism for the observed resistance of normal HSCs and leukemic stem cells (LSCs) to anti-proliferative chemotherapy. Recent studies have revealed cytokines such as Interferon-alpha (IFNα) and G-CSF as well as arsenic trioxide (As(2)O(3)) to be efficient agents for promoting cycling of dormant HSCs and LSCs. Most interestingly, such cell cycle activated stem cells become exquisitely sensitive to killing by different chemotherapeutic agents, suggesting that dormant LSCs in patients may be targeted by a sequential two-step protocol involving an initial activation by IFNα, G-CSF or As(2)O(3), followed by targeted chemotherapy.
Essers
Marieke Alida Gertruda
MA
HI-STEM (Heidelberg Institute for Stem Cell Technology and Experimental Medicine), Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg, Germany. marieke.essers@hi-stem.de
Trumpp
Andreas
A
D000970:Antineoplastic Agents / Q000494:pharmacology; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D007938:Leukemia / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology*; D010087:Oxides / Q000494:pharmacology
D000970:Antineoplastic Agents; D001152:Arsenicals; D016898:Interferon-alpha; D010087:Oxides; D016179:Granulocyte Colony-Stimulating Factor; D000077237:Arsenic Trioxide