Baseline p53 and p21 induction in primary CLL cells shows distinct patterns. (A) The p53 response, defined as p21 induction versus baseline p53 levels (n = 59). Every dot represents 1 patient sample; the cutoffs are depicted by the dashed lines. A distinct pattern can be observed, with the normal response in the top left quadrant, the type-B defect in the bottom left quadrant, and the type-A defect in the bottom right quadrant. Whereas the type-A defect is strongly associated with 17p deletions and TP53 mutations, some samples with the p53 aberration can also be found among the cases with type-B defect and normal response. ○, 17p deletion; ■, sole TP53 mutation; •, no 17p deletion or TP53 mutation. (B) The clone size of the TP53 mutations (irrespective of 17p deletion) was negatively correlated with the level of p21 induction (r2 = 0.5359, P = .0044; cases with missense mutation only). (C) Top panel, p21 induction versus baseline p53 levels for patients with the 11q deletion (n = 12, right panel) and patients without the 17p deletion, the 11q deletion, or the TP53 mutation (n = 22, left panel). A minority of cases in both subgroups show impaired p21 induction with normal baseline p53 expression when based on the determined cutoff. Bottom panel, p21 induction versus p53 induction in patients with the 11q deletion (right) and in patients without the 11q deletion, 17p deletion, or TP53 mutation (left). p21 and p53 show a stronger induction after DNA damage in patients without the 11q deletion, the 17p deletion, or the TP53 mutation (median, 177.9) compared with samples with the 11q deletion (median: 151.7; P = .15).
