Oncogene’s Role in Stem Cell Differentiation Predicts Tumor Aggressiveness

Researchers identified specific oncogenes’ role in stem cell division, whichcould lead to a novel way of interfering with the uncontrolled cell growth that is characteristic of cancer.

Stem cells normally divide in two ways, symmetrically and asymmetrically. In symmetric division, a stem cell either splits into two copies of itself or into two new cells that are committed to a particular tissue type. In asymmetric division, a stem cell divides into one stem cell and one mature cell.

In the current experiments, investigators focused on blood-forming stem cells in mice. Once they had determined that they were actually seeing symmetric and asymmetric division as it occurred, the researchers added different oncogene proteins to the system and documented what happened. One oncogene—Bcr-Abl, which is associated with chronic myelogenous leukemia, a slow-growing cancer that can often be managed—increased the rate of cell division, yet had no effect on the symmetry of the division. Another oncogene, Nup 98-HoxA9, which is associated with the acute form of leukemia, significantly increased the rate of symmetrical division.

When the oncogene makes symmetric division the dominant form, the resulting cells tend to be immature and undifferentiated, report the researchers. Immature cells also tend to be more aggressive in their growth and are often the primary cell type within a cancer, explained the investigators. 

The research was conducted by scientists at Duke University Medical Center, the University of Michigan, and Johns Hopkins School of Medicine. The study is published in Cell Stem Cell.