In CLL, fludarabine refractoriness may be explained by TP53 disruption in ~40% of patients, while ~60% high risk CLL do not present TP53 abnormalities.34 Intriguingly the distribution of BIRC3 disruption and TP53 abnormalities is mutually exclusive and BIRC3 abnormalities can recapitulate the genetics of ~40% chemorefractory and TP53 wild type CLL. The gene discussed is BIRC3; the disease is B-cell chronic lymphocytic leukemia.