Direct in vivo evidence for B-cell receptor and NF-KB activation in mantle cell lymphoma: role of the lymph node microenvironment and activating mutations. [RNA-Seq]

We provide direct in vivo evidence for activation of the BCR and canonical NF-KB pathways in MCL that, in the absence of activating mutations, is dependent on the lymph node microenvironment. This finding provides a mechanistic explanation for the surprising efficacy of ibrutinib for the treatment of this type of lymphoma. Mutations in components of the BCR and NF-KB pathways are associated with cell-autonomous signaling and resistance to ibrutinib. Lymph node biopsies and peripheral blood samples were obtained from patients with previously untreated MCL.