New research from the University of California’s San Diego (UCSD) School of Medicine has identified a protein that is named, Lis1 that is needed for hematopoietic stem cell formation as well as leukemia cells. The discovery has the potential of being a new target in the treatment of leukemia and may provide more effective methods of chemotherapy as the protein regulates and sustains the cell’s growth.
The research was conducted in mice and human leukemia cells with the findings published today in the journal called, Nature Genetics. Researcher, Tannishtha Reya, a UCSD Department of Pharmacology professor, was the studies senior author along with the first authors of the study, Takahiro Ito and Bryan Zindahl. What the team exposed was the close relationship between stem cells and the leukemia cancer cells.
The team deleted the Lis1 protein from hematopoietic stem cells in the mouse which caused an excessive differentiation that depleted the reserve of the undifferentiated stem cells. The lack of this reserve then caused a loss of cells that are specialized for forming new blood. This test finally ended in a “bloodless mouse” that was lethal and resulted in the mouse embryos dying before reaching birth.
The study then went on to examine mice leukemia models with the Lis1 protein when it was turned off. The control mice were give blast-crisis chronic myeloid leukemia (CML) and then the mice were treated with the drug tamoxifen. These mice all died, but mice given the same type of leukemia with cells that were engineered to lose the Lis1 protein did not develop into leukemia in the mice.
The natural history of progression for CML starts from a relatively benign chronic phase into a fatal blast-crisis which resembles acute leukemia but it is incurable and does not respond to conventional chemotherapy.
Reya stated in a UCSD press release that their study shows that the elimination of the Lis1 protein inhibits the growth of the cancer and also identifies the protein and other regulators of protein inheritance as a newer class of molecules that can potentially be targeted in some cancer therapies.
The hematopoietic stem cells are the type of cells that start out all other blood cells. The Lis1 protein will regulate the asymmetric division of those stem cells and eventually assures that the stem cells correctly differentiate and are able to deliver a sustained and adequate supply of new blood cells.
The asymmetric cell division occurs when a stem cell divides into unequal inheritance. One of the new cells differentiates into a permanent specialized cell while the other cell remains undifferentiated and is capable of dividing further.
Reya said that the process is very important for proper generation of all the cells that are needed for the function and development of many normal looking tissues. When a cell divides the Lis1 protein controls the orientation of the mitotic spindle which is an apparatus of sub-cell fibers that segregates chromosomes during the cells division. During the cell’s division the spindle is attached to a point on the membrane of the cell which determines the axis of where the cell with divide. Because the cell does not evenly distribute the protein in the cell, the divisions are often uneven in the division of the proteins.
The study of the stem cell and leukemia cell link has possibly exposed some new types of treatments in the fight against leukemia cancer cells.
By Brent Matsalla