Silvia Deaglio, M.D., Ph.D. University of Torino, Medical School (Italy)

BIOLOGY

CD38 and the fate of CLL cells: innocent bystander or culprit?

Grant awarded in 2006

Abstract:

Several decades of experience in the management of CLL patients clearly indicate that the clinical behavior of this chronic leukemia is highly heterogeneous, with some patients requiring treatment from the start while others do not. One of today's most important challenges in CLL management is to rapidly and correctly identify high-risk and low-risk patients and consequently to choose the best therapy for the individual's particular variant of the disease, while minimizing the adverse effects of drugs.

Today, patients with aggressive CLL can be identified by molecular markers such as the status of the immunoglobulin genes, the presence of CD38 (a surface receptor which may be expressed by the leukemic cells) and of ZAP-70 (a signaling element which may be present inside the cells).

In previous studies, our lab analyzed the role of CD38 expression in CLL and how its interactions with the microenvironment can lead to tumor proliferation. We now propose to show that CD38 and ZAP-70 are part of the chain of events that leads to the complex mechanisms which maintain leukemic cell growth, defeating the normal control mechanisms. This goal will be achieved by means of biochemical, morphologic and functional analyses, which will show how CD38 and ZAP-70 function, where they are localized in the cell and how they interact with one another.

A third part of the project is centered on the CD38 gene. Two forms of the gene have been described in healthy individuals and we wish to see if there is a privileged association between one of the CD38 variants and a CLL subtype.

We hope to apply what we learn in the laboratory about modulating CD38 and ZAP-70 to our clinical treatment decisions.