Aberrant CXCR4 signaling in lymphoma

The CXCR4-CXCL12 pathway regulates migration and proliferation of hematopoietic stem and progenitor cells in the bone marrow niche and is essential for normal B-cell lymphopoiesis. We have established a first-in-man targeting of CXCR4 by a CXCR4-specific peptide. This proposal aims at identifying the role and mechanisms of aberrant CXCR4 activity in lymphomagenesis including novel mouse models, forward genomic screening, analysis of disturbed BCR signaling and resistance mechanisms towards BCR pathway targeting drugs. Aberrant CXCR4 expression and function is also recurrently observed in solid tumors, where it is associated with cancer cell dissemination and poor prognosis. The project will thus extend the studies to solid cancer models within this CRC.