Increased lymphocyte proliferation and survival in CLL dependent upon constitutive activation of several NF-κB pathway genes including MYD88, RIPK1, NRAS, KRAS, CARD11, IRAK4, PIK3CA, and TRAF3

Authors of this abstract conducted experiments to explore the implications of these mutated NF-κB pathway genes

Apoptotic resistance noted in CLL cells harboring RIPK1 Q375, RIPK1 K559R, KRAS Q61H, CARD11 E756K, IRAK4 K400E, and PIK3CA I143V mutations in cell survival assays with or without IgM pretreatment

Treatment with SN50, an NF-κB inhibitor, induced cell death in CLL cells harboring MYD88 L265P mutation while those with RIPK1 Q375, RIPK1 K559R, CARD11 E756K, and PIK3CA I143V were resistant

Similarly ibrutinib, a novel BTK inhibitor, failed to induce cell death in CLL cells with RIPK1 Q375 and KRAS Q61H mutations