Researchers have identified a gene that controls the rapid production and differentiation of the stem cells that produce all blood cell types -- a discovery that could eventually open the door to more streamlined treatments for leukemia and other blood cancers, in which blood cells proliferate out of control.
Additionally, in investigating the mechanisms of this gene, the scientists uncovered evidence that could lead to a protocol for bone marrow transplants that could boost the chance of a cure in some patients.
The research, led by Emmanuelle Passegué, PhD
, of the University of California, San Francisco, demonstrates that the JunB gene is at the center of a complex network of molecular and environmental signals that regulate the proliferation and differentiation of hematopoietic stem cells, the multipotent, self-renewing cells that give rise to all blood cell types.
In the study published April 7, 2009, in the journal Cancer Cell, Passegué's team studied the behavior of JunB-deficient HSCs in both the culture dish and when transplanted into mice.In every case in which engraftment of the HSCs occurred in the mice, the scientists noted a progressive expansion of the myeloidlineage, which constitutes a type of mature white blood cell that fights infection. This expansion led by 6 to 12 months post-transplantation to the development of a myeloproliferative disease, which can evolve to leukemia. The finding indicated that the proliferating JunB-deficient HSCs causes leukemia.
Like traffic lights, which limit speed, direct the flow of vehicles and prevent accidents, JunB curtails both the rate at which HSCs are proliferating and the rate of differentiation toward the myeloid lineage that ultimately results in leukemia. The striking analogy inspired the image for the cover of Cancer Cell's April 7 issue.
Without JunB, HSCs lose their ability to respond to signals from the protein receptors Notch and TGF-beta, which reside on the cells' surface and play critical roles in determining cell fate.
Read more at Jennifer O'Brien, UCSF News Services