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

Abstract:

The aim of the project is to understand the elements responsible for the clinical presentation and the natural history of CLL. In addition to "causal genes", there are a number of other "influential genes" involved in the presentation of CLL. All of these genes interact with the microenvironment to induce proliferation, survival and clonal expansion of CLL cells within the tissues. We hope to identify molecules and mechanisms that can be exploited as potential therapeutic targets.

Under this grant, we have started defining the role of the HS1 molecule in the regulation of leukemic B-cell framework. The HS1 molecule controls the leukemic cell traffic, migration and homing to specific tissues. We have also established two new mouse models. The first model is a cross of two models and suggests that HS1 influences the movement and replication of leukemic cells. The second model is created by injecting the CLL cell line, MEC-1, into adult immunodeficient mice. Both of these models may prove to be useful tools to explore the leukemic tissue microenvironment and its interactions with CLL cells.