Microscopic examination of blood and bone marrow smears is pivotal in understanding and diagnosing hematological disorders. It allows pathologists to identify abnormalities in cell morphology, such as the presence of immature cells, abnormal cell sizes and shapes, or unusual granularity. However, addressing cases with only subtle morphological changes can be challenging and may be prone to inter-observer variabilities, even when reviewed by experienced hematopathologists. We aim to explore the potential of imaging flow cytometry as an innovative diagnostic approach in hematological malignancies, in particular myelodysplastic syndrome and acute myeloid leukemia. The technology leverages high-parameter analyses of thousands of cells at the single-cell level from conventional multicolor flow cytometry with morphological and spatial information from microscopy. This integration markedly augments the statistical robustness and sensitivity of the technology when compared to traditional microscopy approaches.

Harnessing the powers of the CRISPR-Cas9 gene editing technology, we aim at applying this cutting-edge technology towards inactivating fusion oncogenes driving malignant diseases. The therapeutic concept utilizes two guide-RNAs targeting non-coding DNA-regions (introns) in the given fusion oncogene. Upon induction of double-strand DNA-breaks at the targeted locations, a major DNA-deletion will occur in the fusion oncogene, leading to its inactivation. Targeting preserved introns, minimizes insertional mutagenesis and other undesirable effects, as well as allowing for off-the-shelf usage. Our research efforts currently focus on adult and pediatric acute myeloid leukemia as well as bone- and soft-tissue sarcoma.