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Status: Bibliographieeintrag

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Verfasst von:Wang, Wenwen [VerfasserIn]   i
 Stiehl, Thomas [VerfasserIn]   i
 Raffel, Simon [VerfasserIn]   i
 Hoang, Thanh Van [VerfasserIn]   i
 Hoffmann, Isabel [VerfasserIn]   i
 Poisa-Beiro, Laura [VerfasserIn]   i
 Saeed, Borhan R. [VerfasserIn]   i
 Manta, Linda [VerfasserIn]   i
 Eckstein, Volker [VerfasserIn]   i
 Bochtler, Tilmann [VerfasserIn]   i
 Wuchter, Patrick [VerfasserIn]   i
 Jauch, Anna [VerfasserIn]   i
 Trumpp, Andreas [VerfasserIn]   i
 Marciniak-Czochra, Anna [VerfasserIn]   i
 Ho, Anthony Dick [VerfasserIn]   i
 Lutz, Christoph [VerfasserIn]   i
Titel:Reduced hematopoietic stem cells frequency predicts outcome in acute myeloid leukemia
Verf.angabe:Wenwen Wang, Thomas Stiehl, Simon Raffel, Van T. Hoang, Isabel Hoffmann, Laura Poisa-Beiro, Borhan R. Saeed, Rachel Blume, Linda Manta, Volker Eckstein, Tilmann Bochtler, Patrick Wuchter, Marieke Essers, Anna Jauch, Andreas Trumpp, Anna Marciniak-Czochra, Anthony D. Ho, Christoph Lutz
E-Jahr:2017
Jahr:May 2017
Umfang:11 S.
Fussnoten:Gesehen am 21.08.2017
Titel Quelle:Enthalten in: Haematologica
Ort Quelle:Pavia : Ferrata Storti Foundation, 2014
Jahr Quelle:2017
Band/Heft Quelle:102(2017), 9, Seite 1567-1577
ISSN Quelle:1592-8721
Abstract:In patients with acute myeloid leukemia and low percentages of aldehyde-dehydrogenase-positive cells, non-leukemic hematopoietic stem cells can be separated from leukemic cells. By relating hematopoietic stem cell frequencies to outcome we detected poor overall- and disease-free survival of patients with low hematopoietic stem cell frequencies. Serial analysis of matched diagnostic and follow-up samples further demonstrated that hematopoietic stem cells increased after chemotherapy in patients that achieved durable remissions. However, in cases that eventually relapsed, hematopoietic stem cell numbers decreased dramatically at the time of molecular relapse demonstrating that hematopoietic stem cell levels represent an indirect marker for minimal residual disease, which heralds leukemic relapse. Upon transplantation in immune-deficient mice cases with low percentages of hematopoietic stem cells of our cohort gave rise to leukemic or no engraftment, whereas cases with normal hematopoietic stem cell levels mostly resulted in multi-lineage engraftment. Based on our experimental data, we propose that leukemic stem cells display an increased niche affinity in cases with low percentages of hematopoietic stem cells. To validate this hypothesis, we developed new mathematical models describing dynamics of healthy and leukemic cells under different regulatory scenarios. These models suggest that the mechanism leading to decreases in hematopoietic stem cell frequencies before leukemic relapse must be based on expansion of leukemic stem cells with high niche affinity and the ability to dislodge hematopoietic stem cells. Thus, our data suggest that decreasing numbers of hematopoietic stem cells indicate leukemic stem cell persistence and the emergence of leukemic relapse.
DOI:doi:10.3324/haematol.2016.163584
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: http://dx.doi.org/10.3324/haematol.2016.163584
 Volltext: http://www.haematologica.org/content/early/2017/05/19/haematol.2016.163584
 DOI: https://doi.org/10.3324/haematol.2016.163584
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:156258376X
Verknüpfungen:→ Zeitschrift

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