Leukemogenesis and Molecular Therapy

Zhixiong Li, Johann Meyer, Adrian Schwarzer, Rena-Mareike Struß, Min Yang

Our group is interested in understanding how receptor protein tyrosine kinases (PTKs) contribute to leukemia development. Receptor PTKs are often deregulated in human cancers, may be important for self-renewal of cancer stem cells and thus represent an attractive target for selective molecular therapy. Our work has focused in part on the neurotrophin receptors signaling pathway. Neurotrophins (NTs) and their receptors play a key role in neurogenesis and survival. The TRK (tropomyosin-related kinase) receptor PTKs (TRKA, TRKB, TRKC) are high affinity NT-receptors that are expressed in a variety of human tissues. However, we and others have recently obtained evidence for a potential involvement of this receptor system in leukemia. To study the TRK pathway and other important cellular networks, we have currently established mouse models for leukemogenesis through altered TRK signalling and performed molecular analysis in primary samples from patients with acute leukemia. Our data suggested that TRKs and their downstream signaling partners (e.g. mTOR) might serve as attractive therapeutic targets in acute leukemias.

Selected own references:  Li et al., Science 2002; Beutel et al., Br J Haematol 2005; Meyer et al., Leukemia 2007; Newrzela et al., Blood 2008; Li et al., Blood 2009

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