Telomere length dynamics in normal hematopoiesis and in disease states characterized by increased stem cell turnover.
Telomeres both reflect and limit the replicative lifespan of normal somatic cells. Immature sub-populations of human CD34+38- hematopoietic stem cell (HSC) can be identified in vitro based on their growth kinetics and telomere length. Fluorescence in situ hybridization and flow cytometry (flow-FISH) has been used to characterize telomere length dynamics as a surrogate marker for HSC turnover in vivo. Investigations in normal steady-state hematopoiesis provided the basis for follow-up studies in model scenarios characterized by increased HSC turnover. Disorders with underlying malignant transformation of HSC (e.g., chronic myeloid leukemia (CML)) can be discriminated from disease states with increased HSC turnover rates secondary to depletion of the stem cell compartment, for example, as in defined bone marrow failure syndromes. In some of these model scenarios, the degree of telomere shortening can be correlated with disease duration, disease stage and severity as well as with response to disease-modifying treatment strategies. Whether increased telomere shortening represents a causal link between HSC turnover, replicative senescence and/or the induction of genetic instability in acquired HSC disorders remains to be shown. However, data from congenital disorders, like dyskeratosis congenita (DKC), suggest that disturbed telomere maintenance may play a role for replicative exhaustion of the HSC pool in vivo.
Brümmendorf
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TH
Department of Oncology and Hematology with Sections Bone Marrow Transplantation and Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. t.bruemmendorf@uke.uni-hamburg.de
Balabanov
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S
D000818:Animals; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology* / Q000503:physiopathology; D009196:Myeloproliferative Disorders / Q000473:pathology* / Q000503:physiopathology; D016615:Telomere / Q000473:pathology*