The Notch pathway is involved in B-cell development (Arruga et al, 2018) and is activated in CLL patients harboring NOTCH1 mutations (Puente et al, 2011; Arruga et al, 2014), conferring them specific biological features and being associated with poorer outcomes (Rossi et al, 2013; Villamor et al, 2013). The gene discussed is NOTCH1; the disease is B-cell chronic lymphocytic leukemia.