Off-targeting oft-targeted CD20 in cHL

Robert H. Lurie Comprehensive Cancer Center.
Blood (Impact Factor: 10.45). 05/2012; 119(18):4095-6. DOI: 10.1182/blood-2012-03-413146
Source: PubMed


LMP1 and LMP2A mimic CD40 and Ig receptors in B cells. The C-terminal cytoplasmic domain of LMP1 contains 2 domains that associate with TNF receptor associated factors (TRAF), TNFR1-associated death domain (TRADD) and receptor interacting protein (RIP) without propagating a death signal inducing canonical and non-canonical NF-kappa B signaling. LMP2A activates B cell signaling by binding the Src family tyrosine kinase Lyn leading to constitutive phosphorylation of LMP2A and the recruitment of the Syk tyrosine kinase to a phosphorylated ITAM where it becomes activated resulting in the activation of the PI3K and Akt pathway. LMP2A also binds E3 ubiquitin ligases in the Nedd4 family.