The poorest treatment outcomes for this disease occur in patients with a congenital predisposition to cancer, who often present an increased risk of severe, life-threatening toxicity from therapy, as well as an increased likelihood of developing a secondary cancer.
This group requires personalized ALL treatment with a new protocol to reduce the risk of adverse events (including late complications of therapy) and improve their survival. The proposed project is an attempt to address these needs by developing diagnostic and therapeutic solutions based on the integration of genotypic data (derived from genome-wide profiling of constitutional variants) with the clinical course of leukemia, in the context of treatment response and complications.
Specific Objective
- To identify patients with an inherited genetic defect predisposing to cancer and compare the course of leukemia in these patients to that of children without congenital defects promoting carcinogenesis.
- Analysis of clonal structural aberrations in ALL cells in patients with identified gene variants predisposing to cancer, further clarification of the biological characteristics of these growths, and selection of potential molecular therapeutic targets.
- Identification of gene variants associated with high risk, defined in the protocol for severe toxicity in response to specific types of therapy and doses of cytotoxic drugs.
- Development of optimal diagnostic procedures for cancer predisposition in children with ALL.
- Selection of candidate gene variants associated with ALL predisposition for functional testing. In-depth biological and clinical analysis of these variants will be developed in a subsequent research project.