Dickkopf-related protein 1 expression in bone marrow of multiple myeloma patients: correlation with bone disease and plasma cell malignancy type
DOI:
https://doi.org/10.32471/exp-oncology.2312-8852.vol-42-no-4.15289Keywords:
DKK 1, immunohistochemistry, multiple myeloma., osteolytic lesionsAbstract
Summary. Background: Previous studies have pointed out the role of dickkopf-related protein 1 (DKK 1) — Wnt inhibitor, which is essential for osteoblast functioning, in the development of osteolytic lesions in multiple myeloma (MM). Aim: To assess the DKK 1 expression displayed by myeloma cells in bone marrow trephine biopsies of patients with and without osteolytic lesions, and in different malignancy grades of the disease. Methods: The expression level of DKK 1 was assessed immunohistochemically in bone marrow of 49 MM patients presented with and without osteolytic lesions (the 1st and the 2nd group, respectively). Results: Levels of weak, moderate, and strong DKK 1 expression were distributed — as 43.33, 27.78 and 25.56%, and 63.91, 18.80, and 1.50%, respectively when evaluating the samples obtained from the 1st group and 2nd group. Statistically significant differences were found when the levels of DKK 1 expression in the 1st and the 2nd group were compared (χ2 = 51; df = 3; p < 0.001). Conclusions: DKK 1 contributes to the development of osteolytic lesions in MM. The present study provides morphological evidence that inhibition in Wnt signaling may lead to bone damage observed in the advanced stage of the disease.
References
Gavriatopoulou M, Fotiou D, Ntanasis-Stathopoulos I, et al. How I treat elderly patients with plasma cell dyscrasias. Aging 2018; 10: 4248–68.
Spaan I, Raymakers RA, van de Stolpe A, et al. Wnt signaling in multiple myeloma: a central player in disease with therapeutic potential. J Hematol Oncol 2018; 11: 67.
Terpos E, Kostopoulos IV, Kastritis E, et al. Impact of minimal residual disease detection by next-generation flow cytometry in multiple myeloma patients with sustained complete remission after frontline therapy. Hemasphere 2019; 3: e300.
Hata H. Bone lesions and macrophage inflammatory protein-1 alpha (MIP-1a) in human multiple myeloma. Leuk Lymphoma 2005; 46: 967–72.
Sezer O. Myeloma bone disease: recent advances in biology, diagnosis, and treatment. Oncologist 2009; 14: 276–83.
Qiang Y, Chen Y, Stephens O, et al. Myeloma-derived Dickkopf-1 disrupts Wnt-regulated osteoprotegerin and RANKL production by osteoblasts: a potential mechanism underlying osteolytic bone lesions in multiple myeloma. Blood 2008; 112: 196–207.
Abe M. Targeting the interplay between myeloma cells and the bone marrow microenvironment in myeloma. Int J Hematol 2011; 94: 334–43.
Kristensen I, Christensen J, Lyng M, et al. Expression of osteoblast and osteoclast regulatory genes in the bone marrow microenvironment in multiple myeloma: only up-regulation of Wnt inhibitors SFRP3 and DKK1 is associated with lytic bone disease. Leuk Lymphoma 2014; 55: 911–9.
Roodman G. Pathogenesis of myeloma bone disease. Leukemia 2009; 23: 435–41.
Liu T, Wu Y, Niu T. Human DKK1 and human HSP70 fusion DNA vaccine induces an effective anti-tumor efficacy in murine multiple myeloma. Oncotarget 2018; 9: 178–91.
Ray S, Khassawna T, Sommer U, et al. Differences in expression of Wnt antagonist Dkk1 in healthy versus pathological bone samples. J Microsc 2016; 265: 111–20.
Heath D, Chantry A, Buckle C, et al. Inhibiting Dickkopf-1 (DKK 1) removes suppression of bone formation and prevents the development of osteolytic bone disease in multiple myeloma. J Bone Miner Res 2009; 24: 425–36.
Bartl R, Frisch B, Fateh-Moghadam A, et al. Histologic classification and staging of multiple myeloma. A retrospective and prospective study of 674 cases. Am J Clin Pathol 1987; 87: 342–55.
Wajs J, Sawicki W. The morphology of myeloma cells changes with progression of the disease. Contemp Oncol (Pozn) 2013; 17: 272–5.
Berenson JR. Therapeutic options in the management of myeloma bone disease. Semin Oncol 2010; 37: 20–9.
Terpos E, Christoulas D, Gavriatopoulou M, Dimopoulos MA. Mechanisms of bone destruction in multiple myeloma. Eur J Cancer Care 2017; 26: doi: 10.1111/ecc.12761.
Terpos E, Berenson J, Cook R, et al. Prognostic variables for survival and skeletal complications in patients with multiple myeloma osteolytic bone disease. Leukemia 2010; 24: 1043–9.
Hameed A, Brady J, Dowling P, et al. Bone disease in multiple myeloma: pathophysiology and management. Cancer Growth Metast 2014; 7: 33–42.
Terpos E, Ntanasis-Stathopoulos I, Gavriatopoulou M, et al. Pathogenesis of bone disease in multiple myeloma: from bench to bedside. Blood Cancer J. 2018; 8: 7.
Ribourtout B, Zandecki M. Plasma cell morphology in multiple myeloma and related disorders. Morphologie. 2015.
Koduri PR, Gowrishankar S, Malladi VK. Variant morphology in multiple myeloma. Indian J Hematol Blood Transfus 2014; 30: 86–7.
Blom J, Hansen OP, Mansa B. The ultrastructure of bone marrow plasma cells obtained from patients with multiple myeloma during the clinical course of the disease. Acta Path Microbiol Scand 1980; 88: 25–39.
van Marion AMW, Lokhorst HM, van den Tweel JG. Pathology of multiple myeloma. Curr Diagn Pathol 2003; 9: 322–7.
Tian E, Zhan F, Walker R, et al. The role of the Wnt-Signaling Antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med 2003; 349: 2483–94.
Diarra D, Stolina M, Polzer K, et al. Dickkopf-1 is a master regulator of joint remodeling. Nature Med 2007; 13: 156–63.
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