From a cohort of 1147 cases, Plevova et al. identified seven cases with both mutated and unmutated clones in which serial studies showed diminution of an IGHV-M clone with persistence of a co-existing IGHV-U clone, resulting in re-classification to U-CLL.44 Clinically, this was associated with progressive lymphocytosis, disease progression and in some cases, the selection of a TP53-defect post therapy. The gene discussed is TP53; the disease is B-cell chronic lymphocytic leukemia.