Blood stem cell study provides new insight into cancer development

The general theory of cancer development holds that the disease occurs because of the accumulation of certain genetic changes within the affected cells. But a recent study by HSCI researchers at Massachusetts General Hospital indicates that “good” cells can become cancerous because of exposure to a “bad” environment within the body—much as a “good” person may turn to crime when exposed to the “bad elements” in a crime-ridden neighborhood.

In their paper in the March 21 edition of the journal Nature, David Scadden, MD, and colleagues reported that normal blood stem cells are dependent upon their environment. “They get their cues from the surrounding ‘neighborhood’ of bone cells,” said Scadden, co-director of the Harvard Stem Cell Institute and co-chair of Harvard’s Department of Stem Cell and Regenerative Biology. “The environment in which the cells develop can make the system go askew.”

Working with mice with normal blood stem cells, Scadden and his team found that when they made a particular genetic alteration in the bone cells surrounding the blood stem cells, the mice developed a condition called myelodysplasia, a blood disease that is often a precursor of acute myelogenous leukemia (AML), a usually fatal form of cancer.

Scadden said it has long been known that a large fraction of patients who develop myelodysplasia do not have any known genetic abnormality in their bone marrow, where blood stem cells reside. “That suggests that it’s not their blood stem cells that are defective, but rather that there’s something wrong with the environment in which these cells reside,” said Scadden.

According to Marc H.G.P. Raaijmakers, MD, PhD, a postdoctoral fellow in Scadden’s lab and the lead author of the Nature report, “Our findings bring new insight into how cancer can emerge, indicating that nearby cells ‘gone bad’ can facilitate a cell becoming malignant.” In this case, the mice developed fatal AML, and were shown to have rapidly developed new genetic injuries in their blood cells after exposure to defective bone cells in their environment.

Scadden and Raaijmakers said that these findings might suggest a new approach for developing cancer therapies by targeting interactions between the cells that become malignant and the “bad” cells in their neighborhoods.