Paving the way for a targeted treatment for leukaemia and other blood cancers, scientists have found a gene called JunB that controls the rapid production and differentiation of the stem cells that produce all blood cell types.
The investigators have also uncovered evidence that could lead to a protocol for bone marrow transplants that could boost the chance of a cure in some patients.
Led by Dr. Emmanuelle Passegue, of the University of California, San Francisco, the research team has shown 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.
Hematopoietic stem cells are the multipotent, self-renewing cells that give rise to all blood cell types.
For the study, the researchers studied the behaviour of JunB-deficient HSCs in both the culture dish and when transplanted into mice.
In every case wherein 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.
After 6 to 12 months of transplantation, the expansion led to the development of a myeloproliferative disease, which can evolve to leukaemia.
The finding indicated that the proliferating JunB-deficient HSCs causes leukaemia, say the researchers.
JunB curtails both the rate at which HSCs are proliferating and the rate of differentiation toward the myeloid lineage that ultimately results in leukaemia.
When JunB is absent, 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/leukemia field," said Passegue.
The study demonstrated that JunB does not affect the cells' potential for unlimited self-renewal.
The study has been published in the journal Cancer Cell.