Our data show that, in CLL cells, the SC-induced upregulation of the intracellular pathways leading to an increased expression and transcriptional activity of HIF-1α (i.e., RAS/ERK1-2 and PI3K/AKT signalling) is fully recapitulated by exposure of leukemic cells to CXCL12, and is completely abrogated by the CXCR4 antagonist AMD3100. The gene discussed is AKT1; the disease is B-cell chronic lymphocytic leukemia.