Soluble RANKL production by leukemic cells in a case of chronic lymphocytic leukemia with bone destruction

Abstract

Receptor Activator for Nuclear Factor j B Ligand (RANKL) is a member of the TNF-a superfamily normally produced by osteoblasts and stromal cells, which activates its receptor RANK present on osteoclasts and osteoclast precursors, thus favoring their differentiation and activity. An aberrant expression of RANKL was previously reported in a proportion of B cell malignancies such as Chronic lymphocytic leukemia (CLL),[1] multiple myeloma (MM)[1] and follicular lymphoma.[2] Signaling via RANKL in CLL and in MM cells induce the release of cytokines involved in disease pathophysiology, including IL-6, IL8 and TNF-a,[1] whereas release of soluble RANKL (sRANKL) was observed in MM cells and was not detected in CLL cells.[1] In line with this, bone destruction is a prominent feature of MM but a rare complication in CLL. We here present a case of CLL with lytic bone lesions displaying an aberrant release of sRANKL by the malignant cells.