Chronic Lymphocytic Leukemia Carry Key for Pathogenic Transformation

The cells of lymphocytic leukemia carry the key for pathogenic transformation. The understanding of these mechanisms could help the medical community to create new therapies with reduced side affects.

Researchers in the group of Prof. Dr. Hassan Jumaa, Centre for Biological Signalling Studies (BIOSS) of the University of Freiburg, Department for Molecular Immunology, have identified a new mechanism that causes immune cells to convert into malignant cancer cells. In Chronic Lymphocytic Leukemia (CLL), one of the most common types of blood cancer in the Western world, cells themselves carry the key for the pathogenic transformation, the scientists report in the journal “Nature”. Understanding these underlying mechanisms could facilitate new therapies with reduced side effects.

In healthy humans, a subgroup of white blood cells, so-called B-lymphocytes, are responsible for producing antibodies that fight infections. Special receptor molecules of B-lymphocytes detect pathogenic agents via the key-lock principle and consequently start producing antibodies. In patients with CLL, however, abnormal forms of these receptors lead to uncontrolled reproduction of malignant B-lymphocytes. As a result, healthy cells of the immune system get repressed.

"Up to now, it was assumed that agents produced in the bodies of patients dock at the receptor and thereby activate CLL lymphocytes”, Jumaa says. “In our study we could show that specific components of the receptors are responsible for the development of CLL.” In B-lymphocytes of CLL patients, receptor components FR2 and HCDR3 are formed in such a manner that they represent key and lock of the receptor. “Hereby, neighboring receptors of the same cells activate each other and trigger a signalling cascade, which finally causes uncontrolled division of cancer cells.”

Currently, approaches like chemotherapy that suppress symptoms in a relatively unspecific manner are applied in CLL treatment. “Based on decoding the molecular basics of CLL, we now strive to translate this knowledge to make it useful for patients”, Marcus Dühren-von Minden says, another author of the study. “It is conceivable to administer numerous copies of the key FR2 to patients, which then dock to the receptors and prevent neighboring receptors to bind at each other. This stops the consequential signalling cascade.” Through this mechanism, the course of the disease could be precluded much earlier than before, and with less side effects.

                                        This video is about targeting B-cell therapy in Lymphoma.

For more http://www.sciencedaily.com/releases/2012/08/120813074019.htm