Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood with approximately 4000 new diagnoses every year in Europe. The prognosis of ALL has greatly improved during the past decades but significant problems still exist. Firstly, some patients are undertreated as indicated by disease relapse which occurs surprisingly often in patients originally classified as ”low-to-intermediate risk” cases. Typically, relapse in these cases is associated with slow early therapy response. On the other hand, many patients are overtreated as previous studies suggest that approximately half of “standard-risk” cases could be cured with markedly shorter chemotherapy. We plan to comprehensively compare this patient group stratified by their early therapy response. We expect that our approach will allow shortening of the chemotherapy of ”true” low-risk patients, and target more specifically the deranged biology causing slow response in others. The study will be a transnational and multidisciplinary effort, combining multi-omics studies in patient samples and preclinical models with development of novel clinical bioinformatics interfaces and innovative high-throughput drug screens. Building on strong expertise in ALL biology, genetics, disease models and data analysis, our consortium will pioneer efforts towards personalized treatment strategies. The developed analysis workflows have applicability across a wide range of diseases beyond pediatric cancer studied here.
