Unraveling the Bone Tissue Microenvironment in Chronic Lymphocytic Leukemia

SIMPLE SUMMARY: Bone remodeling requires a delicate balance between bone-forming osteoblasts and bone-resorbing osteoclasts. However, in pathological conditions, bone remodeling is often deregulated and the uncoupling of osteoclast and osteoblast functions may alter the extent of bone loss. Although in chronic lymphocytic leukemia (CLL), patients’ macroscopic skeletal involvement appears to be rarer than in other lymphoproliferative diseases, recent studies highlighted that the active crosstalk between leukemic B cells and bone tissue components may lead to the alteration of bone homeostasis already at early stages of the disease, becoming further evident in the advanced stages. Since the pathogenesis of bone involvement in CLL is not completely understood, this manuscript provides an overview of the clinical and biological data related to bone erosion in this disease. ABSTRACT: Chronic lymphocytic leukemia (CLL) is the most frequent leukemia in Western countries. Although characterized by the progressive expansion and accumulation of leukemic B cells in peripheral blood, CLL cells develop in protective niches mainly located within lymph nodes and bone marrow. Multiple interactions between CLL and microenvironmental cells may favor the expansion of a B cell clone, further driving immune cells toward an immunosuppressive phenotype. Here, we summarize the current understanding of bone tissue alterations in CLL patients, further addressing and suggesting how the multiple interactions between CLL cells and osteoblasts/osteoclasts can be involved in these processes. Recent findings proposing the disruption of the endosteal niche by the expansion of a leukemic B cell clone appear to be a novel field of research to be deeply investigated and potentially relevant to provide new therapeutic approaches.