Interestingly, SMAD6 and SMAD7, the two inhibitors of TGFß signalling47,48 are also among the genes identified within the EZH2−/SMAD2–4+ fraction, arguing for a short window of activation of this signal as suggested by the observed variability in CLL response to TGFß1 in vitro. Here, EZH2 is linked to B-cell chronic lymphocytic leukemia.