The molecular signature of AML with increased ALDH activity suggests a stem cell origin
Enrichment of leukemic blasts with a stem cell phenotype correlates with poor survival in acute myeloid leukemia (AML). In this context, measurement of the stem cell marker aldehyde-dehydrogenase (ALDH) activity can distinguish poor prognosis cases with increased fractions of ALDH-positive cells (AL...
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| Hauptverfasser: | , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
16 Jan 2018
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| In: |
Leukemia and lymphoma
Year: 2018, Jahrgang: 59, Heft: 9, Pages: 2201-2210 |
| ISSN: | 1029-2403 |
| DOI: | 10.1080/10428194.2017.1422862 |
| Online-Zugang: | Verlag, Volltext: https://doi.org/10.1080/10428194.2017.1422862
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| Verfasserangaben: | Rachel Blume, Eugen Rempel, Linda Manta, Borhan R. Saeed, Wenwen Wang, Simon Raffel, Olga Ermakova, Volker Eckstein, Vladimir Benes, Andreas Trumpp, Anthony D. Ho & Christoph Lutz |
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| 520 | |a Enrichment of leukemic blasts with a stem cell phenotype correlates with poor survival in acute myeloid leukemia (AML). In this context, measurement of the stem cell marker aldehyde-dehydrogenase (ALDH) activity can distinguish poor prognosis cases with increased fractions of ALDH-positive cells (ALDH-numerous AML) and favorable outcome cases with low percentages (ALDH-rare AML). It has been shown that ALDH-numerous AML favor leukemic engraftment in xenotransplantation assays which suggests increased leukemic stem cell (LSC) potential. To test if this reflects an immature cell of origin, comparative gene-expression studies of CD34+ leukemic blasts were performed. This analysis revealed increased expression of LSC and HSC signatures in ALDH-numerous AML, whereas ALDH-rare AML were enriched for a progenitor signature. The enrichment of stemness-associated transcriptional programs suggests that ALDH-numerous AML derive from immature hematopoietic progenitors and offers an explanation for the poor prognosis and therapy resistance of this subgroup which is likely caused by inherited stem cell properties. | ||
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