Researchers have identified a gene, the rapid production and differentiation of stem cells, all types of blood – a discovery, later the door to further rationalization of treatment for leukemia and other cancers of the blood in the proliferation of blood cells of control.
Furthermore, when studying the mechanisms of this gene, scientists found that the evidence could lead to a protocol for the bone marrow transplants, better chances of recovery in some patients.
The research, led by Emmanuelle Passegu, PhD, University of California, San Francisco, shows that the JunB gene is at the center of a complex network of environmental and molecular signals, proliferation and differentiation hematopoietic stem cells, the multipotent, self-renewing cells, all types of blood cells.
In the study of 7th April 2009 in the journal Cancer Cell, Passegu team is studying the behavior of JunB-HSCs poorly in culture and skin transplantation in mice. In all cases, in the engraftment of HSCs in mice, scientists found a progressive expansion of the myeloid line, which is a type of mature white blood cells that fights infection. This extension of the line 6 to 12 months after transplantation, the development of a myeloproliferative disease that develop, for leukemia. The finding that the exploding JunB-mal HSCs causes of leukemia.
As the traffic lights, the maximum speed, the flow of vehicles and accident prevention, JunB to reduce the rate of the HSCs growing number and percentage of myeloid differentiation in the direction of the line, the end of the leukemia. The strong analogy inspired the image of the coverage of the cancer cell is the April 7 issue.
Without JunB, HSCs lose their capacity to respond to signals from the receptor protein Notch and TGF-beta on the cell surface and critical role in determining cell fate.
“With the discovery of this mechanism, we may one day determine the difference between normal and leukemia stem cells HSCs in gene therapy regulatory networks. This may enable us to develop targeted therapies. Such therapeutic applications are still ahead on the track, but they may very quickly in the blood of leukemia, “says Passegu.
Passegu study represents a milestone in other research, which showed that mutations HSC, leukemia burning HSCs in a faster than normal. However, this study shows that JunB did not affect the cell potential for unlimited self-renewal.
Researchers have demonstrated in two JunB-deficient mice and the mice fight against the powerful chemotherapy drug 5-FU, the depletion of HSCs regeneration. As expected, JunB-deficient mice is more consistent of the myeloid line of control, with constant renewal JunB-mal HSCs myeloproliferative disease that after treatment. When the researchers report in the chances of survival of animals in several cycles of treatment, they found it difficult to distinguish between the two groups, which means that poorly-JunB HSCs not deplete faster than the control HSCs.
In pursuit of the difference between JunB-deficient mice and the control group showed that of the researchers, that the purity of HSCs was an important factor in the success of the growth of new stem cells. First, scientists from the difference between engraftment JunB-mal control HSCs and HSCs. But with the use of SLAM cells, a high degree of purity HSC population, they found that the two groups, in fact, identical engraftment.
This can be a significant impact for patients, the transplantation of bone marrow or leukemia, lymphoma, multiple myeloma and certain types of cancer.
“Currently, there are patients, bone marrow transplants can not quite silence, transplanted HSCs that are optimal for successful engraftment,” says Passegu. Using a highly purified HSC population could be an advantage. “
