Citations

Bone marrow is a complex organ responsible for the regulation of hematopoietic cell distribution throughout the human body. Patients receiving antineoplastic agents as a therapeutic intervention for hematologic malignancy often experience varying degrees of myelotoxicity. Antineoplastic agents cause hypocellularity in marrow resulting in a reduction in hematopoietic tissue activity and a corresponding decline in cell production. Quantifying the adverse effects on hematopoiesis is based on the properties of a single agent, the use of individual drugs within a combination chemotherapy regimen, and the course, or courses, of chemotherapy designed to treat cancer. The direct or indirect suppression of erythrocytes, granulocytes, and megakaryocytes has potential for multiple negative clinical consequences ranging from increased monitoring of blood counts to life-threatening infection and death. This review will provide an overview of the structure and function of competent adult bone marrow, describe the process of hematopoiesis, and characterize the myelotoxicities associated with common antineoplastic agents currently used in the treatment of cancer.

AbstractHematopoietic stem cell (HSC) self‐renewal is regulated by osteoblast and/or endothelial cells within the hematopoietic niche. However, the true identity of the supporting cells and the nature of the secreted factors remain uncertain. We developed a novel mouse model and analyzed whether circulating human peripheral hematopoietic lineage negative/AP+ (lin−/AP+) cells support hematopoiesis in vivo. Thus, immunocompromised (Rag) mice expressing thymidine kinase (Tk) under the control of the 3.6Col1α1 promoter (Tk‐Rag) were treated with ganciclovir, resulting in osteoblast progenitor cell ablation and subsequent loss of hematopoiesis (evaluated by measuring mouse Ter119+ erythroid cells). Following hematopoietic cell depletion, human bone marrow‐derived marrow stromal cells (MSCs) or lin−/AP+ cells were infused into Tk‐Rag mice and compared with saline infusions. Ganciclovir significantly reduced (7.4‐fold) Ter119+ cells in the bone marrow of Tk‐Rag mice compared to saline injections. Infusion of either MSCs or lin−/AP+ cells into ganciclovir‐treated mice resulted in a 3.3‐fold and 2.7‐fold increase (P < 0.01), respectively, in Ter119+ cells compared to mice receiving saline. Relative to lin−/AP− cells, lin−/AP+ cells expressed high levels of mesenchymal, endothelial, and hematopoiesis supporting genes. Thus, human peripheral blood lin−/AP+ cells represent a novel cell type capable of supporting hematopoiesis in a manner comparable to MSCs. J. Cell. Biochem. 116: 58–66, 2015. © 2014 Wiley Periodicals, Inc.

Hypoparathyroidism is a rare disorder that may be acquired or inherited. Postsurgical hypoparathyroidism is responsible for the majority of acquired hypoparathyroidism. Bone disease occurs in hypoparathyroidism due to markedly reduced bone remodeling due to the absence or low levels of parathyroid hormone. Chronically reduced bone turnover in patients with hypoparathyroidism typically leads to higher bone mass than in age- and sex-matched controls. Whether this increased bone density reduces fracture risk is less certain, because while increased bone mineralization may be associated with increased brittleness of bone, this does not appear to be the case in hypoparathyroidism. Treatment of hypoparathyroidism with recombinant parathyroid hormone may reduce bone mineral density but simultaneously strengthen the mechanical properties of bone.