Daniel Mertens: "Dissecting Networks for Microenvironment-Induced Survival in Primary Leukemia Cells"

Daniel Mertens
Mechanisms of Leukemogenesis, University Hospital Ulm + DKFZ Heidelberg

Dissecting Networks for Microenvironment-Induced Survival in Primary Leukemia Cells

In leukemogenesis, genetic and epigenetic lesions are complemented by leukemia-specific interactions with the non-malignant microenvironment. Chronic lymphocytic leukemia (CLL) is an excellent model system to investigate the synergy of intracellular pathomechanisms with the leukemogenic microenvironment. Although CLL is the most common leukemia in the western world, the underlying pathomechanism remains mostly unclear. In addition to intracellular defects, the microenvironmental niche is important as a functional unit required for proliferation and survival of tumor cells. The dependence of the CLL cells on pro-survival support from the microenvironment is apparent from the induction of apoptosis in primary CLL cells when they are cultured without support. We have characterized this microenvironmental stimulation by a candidate gene approach, in which the interaction of pro-survival ligand-receptor pairs and their dose-response curves in primary CLL cells and non-malignant B-cells are quantitated. In parallel, an investigation by gene expression profiling (GEP) kinetics is conducted both in malignant CLL cells after microenvironmental stimulation and in the non-malignant cells that support CLL cell survival.