Functional and Therapeutic Relevance of CD56(NCAM) Expression in Multiple Myeloma.
Stefan Gattenlohner, Anja Mottok, Thorsten Stuhmer, Ralf Bargou, Hermann Einsele, Hans-Konrad Muller-Hermelink. Institute fo Pathology, Medical University of Graz, Graz, Germany; University of Würzburg, Germany; Institute of Pathology, University of Würzburg, Germany
Background: The neural cell adhesion molecule and signal transducer CD56 (NCAM) is an essential marker for abnormal plasma cells and is expressed in ∼70% of multiple myelomas (MM) with impact on tumor progression and osteolyes, but neither the expression profile nor the functional relevance of CD56 isoforms in MM has been investigated.
Design: RNAse Protection Assay, radioactive qRT-PCR, Western Blot, immunofluorescence, cell transfection and generation of stable transfectants, siRNA knock down, cDNA microarrays.
Results: Using new CD56 specific qRT-PCR strategies and antibodies, we could show that CD56140kD is the exclusively expressed CD56 isoform in MM and is associated with the progression of MGUS to manifest MM. Moreover myeloma cell lines stably overexpressing the recently by us identified CD56 mutation/polymorphism Gln/Gly599Arg present in 100% of multiple myelomas showed 6-fold decrease of apoptosis and activation of CD56 dependent kinase signalling cascades such as erk, AKT and CamKII.
Conclusions: We conclude that CD56 expression in MM has impact on tumor progression and activation of anti-apoptotic/pro-proliferative pathways. Therefore CD56 dependent signalling pathways but also CD56 itself regarding the Gln/Gly599Arg mutation/polymorphism might be potential targets for novel immunotherpeutical strategies in MM.
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 240, Tuesday Morning