CLL Global Research Foundation

Neil E. Kay, M.D.
Mayo Clinic

CLL-STROMA INTERACTION

CLL Microenvironment: Role of Mesenchymal Stomal Cells in Disease Progression

Update:

To more completely understand the nature and extent of the influence of leukemic cells we have developed a culture system from the bone tissue of CLL patients. We are able to consistently grow out from the bone tissue a specific type of stromal cell (cells known to make up the structure of the microenvironment of CLL) from both CLL patients and normal volunteers. These cells are called "mesenchymal stem cells", or MSC, and are a known constituent of the stroma in the bone marrow of humans.

Using this culture system, we have found that the leukemic cells and these MSC are able to "talk to each other" and influence each other's behavior. For example, the MSC are able to induce a longer life span for the leukemic B cell and also confer on it more of an activation status which could be related to disease progression.

In contrast, we have found that the leukemic B cells from the CLL patient can activate the MSC through specific types of secreted factors. This activation, we believe, leads to the secretion of more molecules into the blood of CLL patients that leads to what is called an "angiogenic phenotype" which is also related to progression of the disease. For example, these angiogenic factors can also help leukemic CLL cells survive, and in the tissue sites where the CLL cells reside, generate more blood vessels that sustain their growth. Since these angiogenic factors can circulate in the blood of these patients, they can influence distant tissue sites that may help in leukemia cell growth or survival.

Thus, we have identified ways that CLL patients may experience disease progression by the cross-talk between malignant cells and their environment. Because we have identified specific factors, signaling pathways and the cells that are affected by this type of interaction, we hope to intervene to block this dialogue between the two cells and in this aspect treat patients more effectively.