UCSD study of cell division in blood stem cells reveals potential new path to fight leukemia

Cell division is an amazing biological process that’s very easy to take for granted during the day-in, day-out work of biomedical research. Keeping your dividing cells healthy in their petri dishes becomes just a necessary task, a means to an end, in order to multiply enough cells to carry out particular experiments.

But in a CIRM-funded Nature Genetics study published this week, a UCSD research team examined cell division itself and identified a protein called Lis1 that not only plays a critical role in blood stem cell function but may also provide a path to developing therapies for blood cancers such as leukemia.

Stem cells are defined by their unique ability to go through asymmetric division in which one daughter cell remains unspecialized and continues to divide indefinitely while the other daughter cell commits to maturing into a specialized cell type, such as a red blood cell.

When the UCSD team deleted the Lis1 gene in mice, they saw an increased frequency of asymmetric division. This resulted in more daughter cells maturing into specialized blood cells and fewer daughter cells replenishing the supply of blood stem cells. This pool of stem cells eventually became depleted and led to bloodless animals that died before birth. Senior author Tannishtha Reya summarized the finding this way in a press release:

What we found was that a large part of the defect in blood formation was due to a failure of stem cells to expand. Instead of undergoing symmetric divisions to generate two stem cell daughters, they predominantly underwent asymmetric division to generate more specialized cells. As a result, the mice were unable to generate enough stem cells to sustain blood cell production.

A failure of blood stem cell expansion may be bad for normal blood system functions but on the other hand a failure of cancer stem cell growth is obviously good news for fighting cancer. And sure enough, when leukemia cells carrying the Lis1 deletion were introduced into mice, the cancer failed to spread since the lack of Lis1 encouraged more asymmetric cell division and the depletion of cancer stem cells.

This result suggests that development of a drug that inhibits Lis1 function could have anti-cancer properties. One big caveat is that such a drug would likely affect normal cell growth as well and, like current cancer drugs, cause toxic side effects. Still, as Reya points out it’s possible the side effects with a Lis1 blocker may be less severe:

A number of commonly used chemotherapy agents target the machinery that controls cell division. Although these agents can be toxic, their effects on cancer cells are much more potent than their effects on normal cells, and so they continue to be used. Agents that target Lis1 might be more specific and less toxic, which would give them significant clinical value.

To learn more about CIRM-funded projects related to leukemia, read our leukemia fact sheet.

CIRM Funding (TG2-01154) 

Todd Dubnicoff