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
a Department of Medicine V , Heidelberg University , Heidelberg , Germany.
b Centre for Organismal Studies , Heidelberg University , Heidelberg , Germany.
Leuk Lymphoma. 2018 Sep;59(9):2201-2210. doi: 10.1080/10428194.2017.1422862. Epub 2018 Jan 16.
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.
具有干细胞表型的白血病母细胞富集与急性髓系白血病（AML）患者的不良生存率相关。在此背景下，干细胞标志物醛脱氢酶（ALDH）活性的测定可区分预后不良的病例（ALDH阳性细胞比例增加，即ALDH高表达AML）和预后良好的病例（百分比低，即ALDH低表达AML）。研究表明，在异种移植试验中，ALDH高表达AML有利于白血病植入，这表明白血病干细胞（LSC）潜能增加。为了检验这是否反映了起源的未成熟细胞，对CD34白血病母细胞进行了比较基因表达研究。该分析显示，在ALDH高表达AML中，LSC和HSC特征的表达增加，而ALDH低表达AML则富含祖细胞特征。干性相关转录程序的富集表明，ALDH高表达AML起源于未成熟造血祖细胞，并为该亚组的不良预后和治疗耐药性提供了解释，这可能是由遗传的干细胞特性引起的。
