Andreas Rosenwald, M.D. University of Würzburg (Germany)

CLL-STROMA INTERACTION

Cellular characterization of the microenvironment in CLL: Who are the key players and how do they look?

Grant Awarded in 2008

Abstract:

Although major advances in the treatment of CLL in the last two decades have led to a considerable increase in the number of remissions, there is still no curative strategy for this disease. CLL is characterized by the accumulation of mature-looking, but functionally incompetent lymphocytes in the blood, bone marrow, lymph nodes and other organs, leading to a replacement of the normal inhabitants of these compartments.

There is growing evidence that survival signals provided from the cellular environment (e.g. T-cells etc.) towards the malignant CLL cells contribute substantially to the accumulation of the malignant cells. Whereas current therapeutic approaches are highly efficient in clearing circulating leukemic cells, residual CLL cells in secondary lymphatic tissues or bone marrow are likely the source of minimal residual disease and relapses. In these compartments, the close contact between CLL cells and accessory cells likely protects CLL cells from spontaneous and drug-induced cell death and thereby governs tumor progression.

The interaction between the CLL cells and accessory cells is currently being investigated in many experimental 'ex vivo' (or outside the body) approaches (laboratory experiments of CLL and accessory cells), but the 'in vivo' situation remains foggy. This research proposal aims at the characterization of the microenvironment in CLL lymph node and bone marrow specimens by in situ (localized) techniques (immunohistochemistry and in situ hybridization). The identification of 'key players' in the microenvironment that prevent cell death of CLL cells and promote their growth will help to develop therapeutic molecules that target the pivotal interaction of CLL cells and their microenvironment.