Paradoxically, in contrast to the classical mutual exclusivity of mutations with direct overlapping functions, EZH2 LoF mutation frequently coexists with ASXL1 mutation (cBioportal: MDS, adjusted P < .001; MPN, adjusted P = .032) in human patients with MDS/MPN1,17 and CMML18 associated with a worse clinical outlook, urging the need for thorough experimental investigations to resolve this dilemma.17 The gene discussed is ASXL1; the disease is myelodysplastic syndrome.