A new approach to treatment of patients with TEL/AML1 acute lymphoblastic leukemia

Leukemia accounts for about 1/3 of all cancers in children. Treatment of acute lymphoblastic leukemia (ALL) has made great advance in recent years, whereby 98% of all treated children are currently in complete remission and more than 80% of them are fully treated. Unfortunately remaining 15-20% of children still relapse. The specific group of ALL consists of patients with the TEL/AML1 fusion gene resulting from translocation t (12; 21) (p13; q22) and is present in approximately 25% of patients with B-precursor ALL. This translocation is considered to be a favorable prognostic feature, a rapid response to the initial treatment and increased sensitivity to the cytotoxic agent commonly used in therapy, L-Asparaginase (L-Asp). In the dissertation thesis we focused on the study of current therapy and potential targeted approach. In the first part we tried to clarify the mechanism of L-Asp effect in this genotypically defined ALL subgroup. The main effect of L-Asp lies in the depletion of asparagine and glutamine in the serum of patients. The anti-leukemic effect is associated with a lower level of asparagine synthetase enzyme (ASNS) specifically in leukemic cells. Previous work has shown the relationship between lower sensitivity of L-Asp and higher ASNS in leukemic cells. However, our results of monitoring the..