The greatest challenge in modern cancer therapies is the emergence of therapy-resistant cancer cells after seemingly successful initial treatment. Single resistant cells can sometimes trigger tumor recurrence and metastasis years after initial treatment, which is typically more aggressive and even more difficult to treat than the initial tumor. Acute myeloid leukemia (AML) is a particularly aggressive blood cancer with a very high relapse rate associated with a subsequent very poor prognosis. The DKTK RiskY-AML consortium brings together oncologists, cancer biologists and computer scientists from six DKTK sites. It will use a range of novel single-cell technologies and data analysis tools to identify the molecular mechanism by which AML cells escape current therapies. RiskY-AML will then use the gained high-resolution insights into the molecular landscape of resistant AML cells to develop new predictive biomarkers and novel therapeutic options to prevent or overcome resistance and relapse in AML patients.