Grant: Project Grant

CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) is the most frequent leukemia of adults in Western countries. Most cases of chronic lymphocytic leukemia are found through routine blood tests. Mechanisms of CLL pathogenesis are not fully described yet. CLL is characterized by the accumulation of cancer cells in the peripheral blood, bone marrow, lymph nodes, and spleen. Clinically, patients present immunodeficiency increasing along with disease progression and signs of autoimmunity. However, CLL is a heterogeneous disease and the clinical course of CLL varies considerably in which the disease progresses rapidly in some patients and slowly with symptoms that develop gradually in others. This results in clinical heterogeneity in terms of patient survival rates whereas variable response to therapy has also been observed between patients. It is thus essential to find appropriate prognostic factors as well as strategies to overcome resistance to current treatment and new therapeutic targets. This project is based on very exciting observations of a link between the expression of a gene named UGT2B17, CLL poor prognosis and drug resistance. This gene is involved in cell metabolism but an intriguing feature is the fact that current data also point towards a potential role of UGT2B17 beyond its usual metabolism function in the cell. This proposal will serve to better understand the function of this novel prognostic marker in CLL as well as its role in resistance to anti-cancer therapy. Eventually, poor prognostic factors such as UGT2B17 could be used to select patients for future clinical trials and identify subgroups that would most benefit from better therapeutic options and likely to relapse after treatment, the mainstay for first line treatment in CLL.