Federico Caligaris-Cappio, M.D. Instituto Scientifico San Raffaele (Italy)

CLL-STROMA INTERACTION

Dissecting the molecular pathways involved in the interactions between microenvironment and CLL cells

Grant Awarded in 2008

Abstract:

Signals coming from the microenvironment or stromal supporting cells work with genetic defects to establish the natural history of CLL and contribute structural growth of the malignant clone. CLL B-cells retain the capacity to migrate into and out of secondary lymphoid organs, such as nodes, to interact with normal bystander cells in tissue microenvironments and to respond to microenvironment-derived signals.

These interactions keep the CLL cells alive and growing. Stromal cells, helper cells and T-lymphocytes appear to be the key microenvironmental elements involved in the onset and progression of the disease. A number of molecules such as Hematopoietic Cell Lineage Specific 1 (HS1) appear to be key players in microenvironmental stimuli, triggering a response in the CLL cells.

The aim of this project is to dissect the molecular pathways involved in the interactions between microenvironment and CLL cells. The project will be have four integrated tasks: 1) Definition of the role of HS1 in cell structure regulation and migration of normal and CLL lymphocytes; 2) Molecular and functional characterization of bystander cells tissue growth centers; 3) Creation of protein maps of CLL cells from different microenvironmental compartments; 4) Analysis in animal models of the role of stroma in the accumulation and spread of CLL cells.