Interestingly, we also reported that HIF-1α, which regulates tumor cell adaptation to hypoxia and to microenvironmental stimuli, is overexpressed in CLL cells from patients carrying IGHV unmutated genes and TP53 alterations, who are typically characterized by poor outcome and resistance to therapy [115,116]. The gene discussed is HIF1A; the disease is B-cell chronic lymphocytic leukemia.