Nowadays, as a result of these prolonged and well-organized research efforts, childhood acute lymphoblastic leukemia (ALL) can be cured in about 80% of patients mainly by the application of intensive combination chemotherapy regimens. Treatment intensity on contemporary clinical protocols for childhood ALL is adjusted according to prognostic factors predicting the risk of ALL relapse. Yet significant numbers of patients still die due to recurrent disease or the toxicity of treatment and long-term toxicity during lifetime of cured children is a major problem. Hence better personalized adjustment of therapy is urgently needed. Thus, current research activities are aiming at extending our molecular understanding of leukemia and host factors in order to even more specifically account for the mechanisms underlying the differences in treatment response and outcome and to finally address the therapeutic needs of the individual child. Recently, through the application of genome-wide analytical approaches, several candidate biomarkers have been identified for childhood ALL. However, to date, not a single of these markers has been implemented in modern treatment protocols, mainly due to sub-optimal study designs only leading to preliminary and
inconclusive results. In the present proposal we will address the most promising of these new potential biomarkers for treatment stratification in childhood ALL – namely IKZF1 deletions, CRLF2-JAK-STAT and Notch1 pathway aberrations, the early T-cell precursor phenotype, and thiopurine methyltransferase genetics – by rigorous methodological approaches securing an improved translation of emerging molecular information into clinical decision making processes in childhood ALL.