Heterogeneity of leukemia stem cell candidates at diagnosis of acute myeloid leukemia and their clinical significance
Leukemia stem cell candidates (LSCC) can be enriched from patients with acute myeloid leukemia by high aldehyde dehydrogenase (ALDH) activity and CD34 expression. We have previously demonstrated the leukemia-initiating activity of ALDHbright cells in xenograft transplantation models, as well as in v...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2012
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| In: |
Experimental hematology
Year: 2012, Volume: 40, Issue: 2, Pages: 155-165.e1 |
| ISSN: | 1873-2399 |
| DOI: | 10.1016/j.exphem.2011.10.005 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1016/j.exphem.2011.10.005 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0301472X11005029 
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| Author Notes: | Dan Ran, Mario Schubert, Isabel Taubert, Volker Eckstein, Frauke Bellos, Anna Jauch, Hui Chen, Thomas Bruckner, Rainer Saffrich, Patrick Wuchter, and Anthony D. Ho |
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| 520 | |a Leukemia stem cell candidates (LSCC) can be enriched from patients with acute myeloid leukemia by high aldehyde dehydrogenase (ALDH) activity and CD34 expression. We have previously demonstrated the leukemia-initiating activity of ALDHbright cells in xenograft transplantation models, as well as in vitro. Applying single-cell long-term culture-initiating cell assays, we have correlated the functional properties of individual cells within this LSCC population and the respective phenotypes. To define their biologic significance, we also analyzed the relationship between LSCC at diagnosis to long-term clinical outcomes. The median percentage of ALDHbright cells among 101 acute myeloid leukemia patients was 0.51% (range, 0.01-12.90%). Single-cell long-term culture-initiating cell assays, followed by genetic analysis of the progeny cells, showed that the leukemia-initiating activity was found in the ALDHbright/CD34high subset and, to a lesser extent, in ALDHbright/CD34low or ALDHbright/CD34− subsets. Nevertheless, the frequency of ALDHbright cells at diagnosis correlated significantly with the persistence of leukemia after induction chemotherapy (n = 84, Spearman R = 0.3261; p < 0.0025). In the multivariate model, frequency of ALDHbright cells was the strongest prognostic marker (p = 0.0095) affecting overall survival (hazard ratio = 9.107). LSCC are heterogeneous and best reflected by ALDH activity. The frequency of ALDHbright cells at diagnosis is a significant prognostic marker for acute myeloid leukemia. | ||
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