TP53 and B-cell chronic lymphocytic leukemia: In order to get an insight into the sensitivity of the functional assay in detecting subclones with TP53 and ATM defects, we mixed varying proportions of RNA from CLL cells from patients with either biallelic TP53 or biallelic ATM defects and a large clone size, with those from a patient with WT TP53 and ATM. The assay was able to detect a functional defect when the defective TP53 and ATM clone compromised around 35% and 45% of the sample, respectively (Supplementary Figure 3).