PUBLIC RELEASE DATE:
5-Dec-2014
Contact: Barbara Bachtler bachtler@mdc-berlin.de 49-309-406-3896 Max Delbrueck Center for Molecular Medicine (MDC) Berlin-Buch
Chronic lymphocytic leukemia (CLL) is among the most frequent leukemias affecting adults in Western countries. It usually occurs in older patients, does not cause any symptoms for a long time and is often only discovered by accident. Despite treatment, relapses frequently occur. The immunologists Dr. Kristina Heinig and Dr. Uta Hpken (Max Delbrck Center for Molecular Medicine, MDC, Berlin-Buch) and the hematologist Dr. Armin Rehm (MDC and Charit - Universittsmedizin Berlin) have now discovered why this is so. In a mouse model they developed, the researchers demonstrated that crosstalk between the cancer cells and a group of stromal cells in the spleen is crucial for cancer growth. At the same time they were able to block the entry of cancer cells into the spleen as well as their proliferation and thus identified new targets for future therapies in humans (Cancer Discovery, doi: 10.1158/2159-8290.CD-14-0096).*
A high number of malignantly mutated B lymphocytes is characteristic for CLL. B cells are normally an important component of the immune system. They produce antibodies with which the body combats pathogens (foreign antigens) and pathogenically modified structures. They acquire their final functionality in the germinal centers of lymphoid organs such as the spleen.
For this purpose, the healthy B cells migrate into the B-cell zone (B-cell follicle) of the spleen and lodge there in the stromal cell niche. There they interact with follicular dendritic cells (FDC). Unlike the similarly named classical dendritic cells, the FDC are not blood cells but rather stromal cells that form a network in the center of the B cell follicle. This stromal cell network lures B cells into it and exposes them to foreign antigens, which the B cells recognize and require for their activation and maturation. Only then are they fit for their task as antibody-producing immune cells.
The B cells enter the "training center" of the lymphoid organs via the messenger molecules of the immune system, the chemokines. They guide the B lymphocytes, which have a receptor on their surface for these chemokines. Leukemia cells, as malignant immune cells, also have these homing receptors on their cell surface to which these chemokines bind, thus enabling them to establish themselves in the stromal cell niche.
In their research project, Dr. Hpken and Dr. Rehm started from the hypothesis that the processes which normally regulate the migration of B lymphocytes into the B-cell follicle are also the reason for the migration of leukemia cells into the lymphoid organs. Hence, within the B-cell follicle the survival and growth of malignant B cells may depend on the contact of the leukemia cells with the FDC.
In CLL, despite chemotherapy or radiotherapy, a relapse with renewed leukemic proliferation in lymphoid tissues can occur because the FDC usually survive chemotherapy or radiotherapy far better than the leukemia cells. If a few leukemia cells escape the therapy - physicians call this minimal residual disease - the FDC ensure that the leukemia cells within the B-cell follicles have optimal growth conditions and proliferate. Dr. Heinig, Dr. Hpken and Dr. Rehm have now elucidated this process in detail in a mouse model, which is similar to human CLL.
Intensive interaction between leukemia cells and the FDC
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