Editors' ChoiceLeukemia

Stem Cells: The Good, the Bad, and the Ugly

See allHide authors and affiliations

Science Translational Medicine  28 Sep 2011:
Vol. 3, Issue 102, pp. 102ec157
DOI: 10.1126/scitranslmed.3003236

There are many different types of stem cells: embryonic, hematopoietic, mesenchymal, endothelial, induced pluripotent… to name but a few. In addition to this list, there is evidence that some cancers may originate from a small pool of so-called cancer stem cells (CSCs). Whether CSCs exist in human patients or whether they are an artifact of animal models is a matter of debate. Like other stem cells, CSCs possess the capacity for self-renewal and the ability to generate differentiated progeny. However, the molecular pathways that regulate CSCs are not clear. In a new study, Eppert and colleagues use gene expression signatures to analyze leukemia stem cells (LSCs) and hematopoietic stem cells (HSCs) in primary samples from patients with acute myelogenous leukemia (AML).

First, the researchers sorted cells from 16 primary human AML samples into four popula­tions according to expression of the cell surface markers CD34 and CD38. Using a mouse xenograft assay, they tested each fraction to see whether they contained LSCs. Surface marker profiling of the primary AML samples revealed that LSCs could not be defined on the basis of the CD34+ CD38 phenotype. Using bioinformatic analysis and a false discovery rate of 0.05, 42 and 121 genes were identified as either LSC-related or HSC-related signatures, respectively. Forty-four genes were found in both signatures and were designated core-enriched HSC-LSC genes. More importantly, when LSC- and HSC-related gene signatures were examined in a cohort of 160 cytogenetically normal AML patients, both signatures correlated negatively with overall survival.

These intriguing results need to be validated in a randomized clinical trial of a large cohort of AML patients. However, these early observations suggest that LSCs exist in AML and that the shared transcriptional profiles of LSCs and HSCs containing the genes for “stemness” are poor prognostic indicators for AML. Not all stem cells are good, and in the war against AML, using bad, ugly LSCs as a prognostic marker may be a valuable strategy in the fight against cancer.

K. Eppert et al., Stem cell gene expression programs influence clinical outcome in human leukemia. Nat. Med. 17, 1086–1093 (2011). [Abstract]

Navigate This Article