The molecular signature of AML with increased ALDH activity suggests a stem cell origin. Issue 9 (2nd September 2018)

• Record Type: Journal Article
• Authors: Blume, Rachel; Rempel, Eugen; Manta, Linda; Saeed, Borhan R.; Wang, Wenwen; Raffel, Simon; Ermakova, Olga; Eckstein, Volker; Benes, Vladimir; Trumpp, Andreas; Ho, Anthony D.; Lutz, Christoph
• Is Part Of: Leukemia & lymphoma. Volume 59:Issue 9(2018)
• Page Start: 2201
• Page End: 2210
• Publication Date: 2018-09-02
• Subjects: Acute myeloid leukemia -- leukemia stem cell -- gene-expression -- ALDH; Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.1080/10428194.2017.1422862
• Languages: English
• ISSNs: 1042-8194

Abstract

Abstract: 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.