Department of Clinical Research (DCR)

Oncology / Haematology (Adults)

Experimental Research Programmes

The molecular pathology of acute and chronic leukemia is being investigated using both cell line models as well as clinical material from patients. Experimental research in the lab is centered on the investigation of the molecular mechanisms underlying the leukemic onset, in particular in acute myeloid leukemia (AML). A hallmark of AML is the accumulation of myeloid precursor cells in the bone marrow. Characteristically, the malignant leukemic cells display a block in their normal differentiation process at particular stages. Research on the pathogenesis of AML is focused on the analysis of oncogenes and tumor suppressor genes which deregulate proliferation and cell death in AML cells. Although the ultimate relationship between altered proliferation and differentiation in AML remains to be elucidated, our current concept indicates that deregulation of the tumor suppressor p53 and the transcription factor CEBPA critically affects both differentiation and apoptosis in AML cells. Novel p53 inducing agents are promising compounds for a targeted AML treatment and clinical studies have been initiated.
A specific focus of our research has been set on AML subtypes characterized by mutations of the myeloid key transcription factor CEBPA. We have investigated both somatic and germline CEBPA mutations leading to sporadic and familial forms of AML. Although familial AML is a rare finding outside of a genetic syndrome, germline mutations appear to be present in up to 10% of AML patients with CEBPA mutations.
A second focus of our research has been the investigation of the endoplasmatic reticulum (ER) stress response as a new mechanism involved in the pathogenesis of AML. Malignant cells of specific AML subtypes show activated ER stress levels. These patients are promising candidates to benefit from ER-stress inducing compounds, and such studies are under way.

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