A Distinct Molecular Signature of Purified Cancer Stem Cells: Evidence for a Hematopoietic Stem Cell Origin of the 5q- Syndrome.

Herein we present the first global gene expression profile of purified cancer stem cells (CSCs). Constituting 0.08% of bone marrow cells, CD34⁺CD38⁻Thy-1⁺ cells represent the CSCs in 5q− myelodysplastic syndromes. The global gene expression pattern of purified 5q− CD34⁺CD38⁻Thy-1⁺ stem cells was overall very similar to the global gene expression of normal hematopoietic stem cells and not progenitor cells, supporting that 5q− stem cells originate in and outcompete normal CD34⁺CD38⁻Thy-1⁺ stem cells. However, a few distinct differences in gene expression distinguish 5q− from normal stem cells and might therefor be of potential pathogenetic importance. BMI1, a critical regulator of self-renewal is up-regulated in most 5q− patients stem cells, which could explain the obvious advantage of the 5q− stem cells over normal stem cells. The myeloid transcription factor CEBPα was clearly down-regulated in 5q− CD34⁺CD38⁺Thy-1⁻ progenitors compared to normal progenitors, consistent with the typical deficient myeloid differentiation seen in 5q− syndrome. In contrast, CEBPα was rather up-regulated in 5q− stem cells from several patients. Thus, these studies demonstrate the importance of specifically identifying, characterizing and eventually targeting CSCs.