The discovery that many p53 pathway genes (i.e. CDKN1A, BBC3/PUMA, PCNA, GADD45A) were activated in CRs but not in NRs provides further support to the notion that fludarabine treatment of patients with CLL induces a p53-dependent gene expression response [27] and that a defective p53 pathway in refractory CLLs, due to 17p deletions, p53 mutations and other p53-linked dysfunctions, is associated with fludarabine resistance [4,25,26,28]. This evidence concerns the gene TP53 and B-cell chronic lymphocytic leukemia.