Deciphering the role of BIRC3 in lymphomagenesis and resistance to therapy

Inactivating mutations in BIRC3 frequently occur in CLL and are associated with poor prognosis and resistance to therapy. BIRC3 encodes for the cellular inhibitor of apoptosis protein 2 (cIAP2) which is an E3 ligase that attaches ubiquitin chains to immune receptor signaling complexes, thereby regulating NF-κB signaling. NF-κB activation is known to provide pro-survival signals to leukemic cells and it induces the release of cytokines that can modulate tumor microenvironment. Therefore, the aim of the present proposal is to understand the role of cIAP2 aberrations in lymphomagenesis, resistance to therapy and tumor microenvironment.