Adaptor protein Lnk binds to PDGF receptor and inhibits PDGF-dependent signaling.

Objective: Platelet-derived growth factor receptors α and β (PDGFRA, PDGFRB) are frequently expressed on hematopoietic cells and regulate cellular responses such as proliferation, differentiation, survival, and transformation. Stimulation by autocrine loops or activation by chromosomal translocation makes them important factors in development of hematopoietic disorders. Interaction with the ligand PDGF results in activation of the tyrosine kinase domain and phosphorylation of tyrosine residues, thereby creating binding sites for molecules containing Src homology 2 domains.

AML1/ETO induces self-renewal in hematopoietic progenitor cells via the Groucho-related amino-terminal AES protein.

The most frequent translocation t(8;21) in acute myeloid leukemia (AML) generates the chimeric AML1/ETO protein, which blocks differentiation and induces self-renewal in hematopoietic progenitor cells. The underlying mechanisms mediating AML1/ETO-induced self-renewal are largely unknown. Using expression microarray analysis, we identified the Groucho-related amino-terminal enhancer of split (AES) as a consistently up-regulated AML1/ETO target.

Construction and application of an inducible system for homogenous expression levels in bulk cell lines.

Stringently controlled conditional expressing systems are crucial for the functional characterization of genes. Currently, screening of multiple clones to identify the tightly controlled ones is necessary but time-consuming. Here, we describe a system fusing Tet (tetracycline)-inducible elements, BAC (bacterial artificial chromosome) and Gateway technology together to allow tight control of gene expression in BAC-transfected eukaryotic bulk cell cultures.

Activation of Wnt signalling in acute myeloid leukemia by induction of Frizzled-4.

Wnt signalling regulates proliferation, self renewal and cell fate. Aberrant Wnt signalling is thought to contribute to AML pathogenesis by enhancing self renewal. Herein, we provide evidence for increased expression of Frizzled-4, a receptor for Wnt ligands, in primary AML blasts compared to normal bone marrow on the protein level.

Activation of Wnt signaling in cKit-ITD mediated transformation and imatinib sensitivity in acute myeloid leukemia.

The Wnt-signaling pathway plays a critical role in directing cell fate during embryogenesis and also in the pathogenesis of cancer. In leukemia, it is well described that activating internal tandem duplications (ITD) mutations in receptor tyrosine kinases like cKit or Flt3 confer to the pathogenesis of cancer. Here, we analyzed whether Wnt-signaling plays a role in cKit-ITD mediated transformation.

Wnt signaling regulates transendothelial migration of monocytes.

The Wnt-signaling pathway plays a critical role in directing cell fate during embryogenesis. Several lines of evidence also suggest a role in inflammatory processes. Here, we analyzed whether Wnt signaling plays a role in leukocyte inflammatory responses.