Mieloma multipel: aspek patogenesis molekuler
Multiple myeloma (MM) is a neoplastic plasma disorder that is characterized by clonal proliferation of malignant plasma cells in the bone marrow, monoclonal protein in the blood or urine and associated organ dysfunction. It is preceded by a premalignant tumor which is share genetic abnormalities, monoclonal gammopathy of undetermined significance (MGUS). Although remarkable progress has been achieved, but pathogenesis of MM is still very complex. Multiple myeloma appears to arise from the malignant transformation of germinal-center B-lymphocyte. The first oncogenic events in MM appear to occur in the germinal center due to error in isotype class switching and somatic hypermutation. MM is divided into two distinct genetic subtypes: (1) hyperdiploid myeloma is characterized by multiple trisomies of chromosome 3, 5, 7, 9, 11, 15, 19 and 21; (2) non-hyperdiploid in contrast is characterized by recurrence translocations t(4;14), t(14;16), t (14;20); t(6;14) and t(11;14). A unifying event in the pathogenesis of MM is the dysregulated expression of cyclin D gene. Genetic aberrations occur in MM and also in premalignant state (MGUS), suggesting that genetic mutations alone are necessary, but not sufficient for myeloma transformation. A “ random second hit model” was proposed. Hypothetical second hits are: additional genetic changes ( RAS mutation, p16 methylation, p53 mutation), proliferation due to cell cycle dysregulation, evasion of programmed cell death and changes in bone marrow microenvironment. A complex interaction with the BM microenvironment , characterized by activation of osteoclast and supression of osteoblast , leads to lytic bone lesions.
2. Dispenzieri A, Lacy MQ, Kumar S. Multiple Myaloma. In: Greer JP, Arber DA, Glader B, List A, Means RT, Paraskevas, Rodgers GM (editors). Wintrobe Clinical Hematology. Thirteen edition. Philadelphia: Lippincott, Williams & Wilkins, 2014.
3. Bergagsel PL, Kuehl WM. Molecular Pathogenesis and a Consequent Classification of Multiple Myeloma. J Clin Oncol 2005;23:6333-6338.
4. Bianchi G, Munshi NC. Pathogenesis beyond the cancer clone(s)in multiple myeloma. Blood 2015;125:3049-3056.
5. Chesi M, Bergsagel PL. Molecular pathogenesis of multiple myeloma:basic and clinical updates. Int J Hematol 2013;97:313-323
6. Bergsagel PL, Stewart AK, Russel J, Fonseca R. Molecular genetic aspects of plasma cell disorders. In: Greer JP, Arber DA, Glader B, List A, Means RT, Paraskevas, Rodgers GM (editors). Wintrobe Clinical Hematology. Thirteen edition. Philadelphia: Lippincott, Williams & Wilkins, 2014.
7. Cogbill CH. Molecular Diagnostics of Multiple Myeloma. www.wmc./Molecular-Diagnostics-Multiple-Myeloma. Diakses 15 April 2018
8. Jaganath S. Pathophysio;logical Underpinings of Multiple Myeloma Progression. J Manag Care Pharm 2008;14(sppl S):S7-S11
9. Bergagsel PF. Molecular Pathogenesis of Multiple Myeloma. www.mayoclinic.pure.elsevier.com/molecular-pathogenesis- multiple- myeloma. Diakses 15 April 2018
10. Rajkumar SV/ Pathobiology of Multiple Myeloma – UpToDate. www.uptadate.com/contents/pathobiology-of-multiple myeloma. Last updated Nov 23, 2017.
11. Kuehl WM, Bergsagel PL. Molecular pathogenesis of multiple myeloma and its premalignant precursors. J Clin Investig 2012;122:3456-3463.
12. Shay G, Hazlehurst L, Lynch CC. Dissecting the Multiple Myeloma-bone microenvironment reveals new therapeutic opportunities. J Mol Med (Berlin) 2016;94:21-25,
13. Terpo E, Stathopoulos IN, Gavriatopoulou M, Dimepoulos MA. Pathogenesis of bone disease in multiple myeloma: from bench to bedside. Blood Cancer Journal 208;8:1-12
14. Kalita LKK, Saikia B. Recent advances in molecular pathogenesis of multiple myeloma – Role of cytokine: Review of literature. Int J Med Health Res 2016;2:43-45
15. Anderson KC. Progress and Paradigms in Multiple Myeloma. Clin Cancer Res 2016; 22:5419-5427.
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