Therapeutic stratification of acute leukemia using high throughput drug screening

The functional patterns from high-throughput drug sensitivity vs. resistant profiles of different diagnostics leukemic samples and at the same time their comprehensive integration to their genetics and transcriptomics profiles can be helpful in better stratification of the existing therapies and finding the novel and overlooked biomarkers. Therefore we map the dependencies on various signalling pathways with a library of (n = 175) compounds, which includes chemotherapeutics in the GPOH recommended treatment protocols for childhood cancer, inhibitors in early/late clinical phase or waiting to enter clinical trials. The automation process of drug and cell dispensing minimize the probability of human induced errors and allows working with limited biopsy or Primografts patient material. Synergistic combinations of drugs are later explored in a combination screen with promising hits. Using this platform (> 100 samples), we have stratified and identified novel Myc related biomarkers using BCR-ABL1+ and T-ALL samples. In another instance we have also employed the platform to measure for individual acute/long term toxicity to chemotherapy in childhood cancer based on genetic predisposition.