We have developed and characterised two mouse Eμ-Myc B-cell lymphoma models of de novo CHK1i resistance, arising from mutations in the c-Rel and RelA NF-κB subunits, alongside cell line models of acquired CHK1i resistance, which underline the critical role that intrinsic target and/or pathway rewiring plays in this context [18,20]. The gene discussed is NFKB1; the disease is B-cell non-Hodgkin lymphoma.