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Gene Protects Against Leukaemia
Leukaemia developed in mice
without the gene JunB;
© NCI Visuals Online
The research demonstrates that the JunB gene is at the centre of a complex network of molecular and environmental signals that regulate the proliferation and differentiation of hematopoietic stem cells (HSC), the multi-potent, self-renewing cells that give rise to all blood cell types.
In the study, the research team studied the behaviour 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 myeloid lineage, which constitutes a type of mature white blood cell that fights infection. This expansion led by six to twelve months post-transplantation to the development of a myeloproliferative disease, which can evolve to leukaemia. The finding indicated that the proliferating JunB-deficient HSCs causes leukaemia.
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 leukaemia.
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.
"By uncovering this mechanism, we might one day be able to determine the difference between normal HSCs and leukemic stem cells in gene regulatory networks. This could allow us to develop more targeted therapies. These kinds of therapeutic applications are still down the road, but they can happen very quickly in the blood and leukemia field," says lead researcher Emmanuelle Passegué.
MEDICA.de; Source: University of California - San Francisco