Lynne V. Abruzzo, M.D., Ph.D. University of Texas MD Anderson Cancer Center

THERAPY/ PROGNOSTIC

Altered expression of genes other than ATM contributes to poor outcome in CLL patients with 11q deletions

Grant awarded in 2009

Abstract:

Deletion of chromosomal material in the long arm of chromosome 11, i.e., del(11q), is identified in about 10-20% of CLL patients and is one of the most important predictors of poor prognosis. This region contains the ATM gene (as well as many other genes), which normally suppresses the growth of tumors. Thus, the poor prognosis of patients with del(11q) has been attributed to deletion of this gene. Recently, we have identified CLL cases with del(11q) in which the ATM gene appears intact. This suggests that genes in this region other than ATM may account for the poor prognosis of these patients.

In our experiments, we will look for differences in messenger RNA and protein expression in CLL samples with and without del(11q). We will look for genes within this region whose known function suggests that they contribute to the aggressive behavior of CLL cases with del(11q). We will then explore the functional outcome of either restoring or knocking-down the expression of these quantitatively or structurally aberrant proteins in primary CLL cells or cell lines. In summary, our goal is to identify dysregulated genes in del(11q) CLL patients, other than ATM, that may promote disease progression and relapse, and require a distinct therapeutic approach.