Impact of intrinsic and extrinsic immune cell signaling on chronic lymphocytic leukemia


Project Summary

Chronic lymphocytic leukemia (CLL) is characterized by an expansion of monoclonal B cells that carry autoreactive B cell receptors and exerts complex alterations within the associated immune cell compartment. Autoreactive B cells would normally undergo negative selection. The proposal aims to define whether mutations that activate NF-κB signaling, in particular MyD88 and Notch1, inhibit negative selection and thereby allow autoreactive B lymphocytes to transform to CLL. Furthermore, this study aims to elucidate the role of NF-κB activation via innate immune receptors in the myeloid cell compartment within the CLL microenvironment.