Emerging evidence suggests that a crosstalk of tumor cells with surrounding immune and accessory cells markedly contributes to the pathophysiology of myeloid neoplasia and B cell malignancies such as acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL). Hereby, proliferation and survival of the leukemia cells depends on a complex interplay of distinct cell types, the extracellular matrix, and soluble factors within the organs, collectively referred to as the tumor microenvironment. Increasing evidence highlights the considerable and thus far underestimated role of the microenvironment in leukemia pathogenesis and stresses the therapeutic value of disrupting these interactions.
It is therefore essential to understand which molecular mechanisms regulate the leukemic infiltration of the organs. We are interested in how chemokine signals converge with CD44 and integrins to be integrated in downstream migratory and adhesive cues during this process. We elucidate how the cytoskeletal machinery is regulated by quiescence or activation of leukemic cells and which components are involved in homing, retention, and proliferation. In particular, we recently reported that the integrin adaptor integrin-linked kinase (ILK) and the Rac activator Tiam1 have a role in centrosome clustering, thus being required for leukemia cell proliferation in CLL. We employ in vivo adoptive transfer models and transgenic mouse models of AML and CLL together with real-time and time-lapse videomicroscopy, immunofluorescence, and cytometrical and biochemical approaches.
Tanja Nicole Hartmann
Laboratory for Immunological and Molecular Cancer Research
Salzburg Cancer Research Institute
Müllner Hauptstraße 48