T-cell acute lymphoblastic leukemia (T-ALL) accounts for 15% of pediatric and 25% of adult ALL cases. Multi-agent combination therapy has intensively improved leukemia-free survival. However, 20% of pediatric and 50% of adult T-ALL still relapse. Thus, further advances in treatment are still needed, requiring a better understanding of disease biology. DNA methylation (5-methyl-cytosine (5mC)) plays a role in biological process, including gene expression and pathogenesis of cancer.
Recently, an oxidative derivative called 5-hydroxy-methy-cytosine (5hmC) has emerged as an important player disrupted in a wide variety of cancer. To date, no data are available in the context of T-cell leukemia. The goal of this research proposal is to investigate 5hmC patterns in T-ALL cell lines and primary leukemia samples, in order to define how DNA hydroxymethylation drives gene expression in T-ALL. We strongly believe these data will complement our molecular genetic understanding of human TALL.