It is conceivable that similar mechanisms that confer resistance to idelalisib may also be pertinent to duvelisib; constitutive activation of MAPK-ERK1/2 signalling, whether through increased phosphorylation of components of this pathway or activating mutations, may compensate for inhibition of PI3-kinase-mediated signalling and promote the survival of CLL cells. The gene discussed is MAPK3; the disease is B-cell chronic lymphocytic leukemia.