The Role of the Wnt-Signaling Antagonist DKK1 in the Development of Osteolytic Lesions in Multiple Myeloma

• Published in: The New England journal of medicine Vol. 349; no. 26; pp. 2483 - 2494
• Main Authors: Tian, Erming, Zhan, Fenghuang, Walker, Ronald, Rasmussen, Erik, Ma, Yupo, Barlogie, Bart, Shaughnessy, John D
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 25.12.2003
• Subjects: Biological and medical sciences; Bone cancer; Bone density; Bone marrow; Bone Marrow - metabolism; Case-Control Studies; Gene Expression; Gene Expression Regulation, Neoplastic; General aspects; Hematologic and hematopoietic diseases; Humans; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunopathology; Intercellular Signaling Peptides and Proteins; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Logistic Models; Magnetic Resonance Imaging; Medical sciences; Multiple Myeloma - complications; Multiple Myeloma - genetics; Multiple Myeloma - metabolism; Mutation; NMR; Nuclear magnetic resonance; Oligonucleotide Array Sequence Analysis; Osteoblasts; Osteolysis - diagnosis; Osteolysis - etiology; Plasma Cells - metabolism; Prostate cancer; Protein Biosynthesis; Proteins - genetics; Proteins - metabolism; Proto-Oncogene Proteins - antagonists & inhibitors; Signal Transduction; Wnt Proteins; Zebrafish Proteins; Medicine; Immunopathology; Signal transduction; Immunoglobulinopathy; Lymphoproliferative syndrome; Development; Malignant hemopathy; Antagonist; Lesion; Myeloma
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa030847

This study found that plasma cells from the bone marrow of patients with myeloma and osteolytic lesions expressed high levels of the DKK1 gene and produced the DKK1 protein, whereas plasma cells from patients without bone lesions did not overexpress the gene or produce the protein. New light on bone lesions in multiple myeloma. Lung, breast, and prostate cancer and multiple myeloma have an affinity for bone, where they cause osteoblastic lesions (prostate cancer) or osteolytic lesions (lung and breast cancer and multiple myeloma). 1 Research on the mechanisms by which multiple myeloma cells induce osteolysis has focused on the osteoclast's role in shifting the normal balance between bone formation and bone resorption in favor of resorption. 2 Bone resorption is blocked by bisphosphonates, 3 but the inability of these compounds to repair lytic lesions indicates that a functional defect of osteoblasts is also important in the lytic process. Indeed, the number and function of osteoblasts are . . .