The purpose of the present study was to evaluate the possible interconnections between the CXCL12/CXCR4 axis and the transcription factor HIF-1α in CLL, and to elucidate the role of HIF-1α regulatory pathways, both at the tumor cells- and SC-level, in the protection exerted by SC towards apoptosis in leukemic cells. Here, CXCR4 is linked to B-cell chronic lymphocytic leukemia.