While investigating the effect of either a c-Rel deletion or RelAT505A phosphosite knockin on the Eμ-Myc mouse model of B-cell lymphoma, we discovered that both NF-κB subunit mutations resulted in CHK1 inhibitor resistance, arising from either loss or alteration of CHK1 activity, respectively. Here, CHEK1 is linked to B-cell non-Hodgkin lymphoma.