Herein, we confirm that the recently described CLL xenograft model in NSG mice supports tumor proliferation at a similar rate as seen in patients.39 In addition, we have expanded the characterization of the model to demonstrate that CLL activation in the murine spleen involves activation of BCR and NF-κB signaling in a similar manner as we have previously described in the human LN.3 Notably, this conclusion is based on direct comparisons of matched tumor samples of the same patients donating the PBMCs used for xenografting. Here, NFKB1 is linked to B-cell chronic lymphocytic leukemia.