Like all cancers, Hodgkin’s disease starts from a single abnormal cell that gets completely out of control, in this case a white blood cell. For any number of reasons, the white blood cell's genes become altered and tell the cell to turn into giant malignant cancer cells and to start dividing out of control.

In Germany up to 2000 children and adults fall ill with Hodgkin’s disease every year. Although today very good curative successes are achieved with chemotherapy and radiation therapy, until now a better targeted, less harsh treatment has not been available. The problem: the causes of the disease are still largely unknown. That is why it is so difficult to develop appropriate new therapies.

Researchers of the German National Genome Research Network have now succeeded in finding out what factors are involved in the genesis of Hodgkin’s disease. In the cell nucleus – i.e. in the central command of the cell – there are unusually high levels of certain growth regulators that take over different gene programs and disable the normal controls over cell proliferation. Some of the growth regulators that evidently win the upper hand in the cell nucleus are "NF-kB", "AP-1", and "Stat 5a".

How do "NF-kB", "AP-1" and "Stat 5a" work?

Cells are constantly sensing their environment and making decisions about when it is appropriate to divide. To do this, they use an intricate signal transduction system that receives, registers and compares the information and relays the orders to the central command of the cell – the cell nucleus, deep in the cell's interior. These signals regulate events that ultimately control the decision to divide.

The three proteins "NF-kB", "AP-1", and "Stat 5a" belong to this system. Messenger substances of the immune system order "NF-kB" to enter into the central command of the cell, whenever pathogens or unknown substances penetrate the body. Having arrived there, "NF-kB" behaves as a relay switch - it activates a defensive program which positions the cells of the immune system to combat their opponents. After the work has been done, the "NF-kB" proteins normally leave the cell nucleus again. But in Hodgkin’s disease they stay in the command centers of the cells.

"It is completely unclear which cellular signals entice the factor into the cell nucleus and why it settles in there to stay," said Professor Claus Scheidereit from the Max Delbrück Center for Molecular Medicine (MDC) in Berlin. His work in the National Genome Research Network deals with the signal systems of tumor cells.

Page 2: "Stat 5a" sees to it that the cancer cell grows and thrives.