切换至 "中华医学电子期刊资源库"

中华临床医师杂志(电子版) ›› 2018, Vol. 12 ›› Issue (11) : 630 -634. doi: 10.3877/cma.j.issn.1674-0785.2018.11.008

所属专题: 文献

综述

多发性骨髓瘤骨病发病机制及治疗的研究进展
金炜1, 管俊1,(), 陈家楠1, 许荟1   
  1. 1. 225001 江苏扬州,苏北人民医院血液科
  • 收稿日期:2018-04-29 出版日期:2018-06-01
  • 通信作者: 管俊
  • 基金资助:
    扬州市社会发展项目(YZ2015052)

Pathogenesis and treatment of multiple myeloma bone disease

Wei Jin1, Jun Guan1,(), Jianan Chen1, Hui Xu1   

  1. 1. Department of Hematology, the Northern People′s Hospital of Yangzhou, Yangzhou 225001, China
  • Received:2018-04-29 Published:2018-06-01
  • Corresponding author: Jun Guan
  • About author:
    Corresponding author: Guan Jun, Email:
引用本文:

金炜, 管俊, 陈家楠, 许荟. 多发性骨髓瘤骨病发病机制及治疗的研究进展[J]. 中华临床医师杂志(电子版), 2018, 12(11): 630-634.

Wei Jin, Jun Guan, Jianan Chen, Hui Xu. Pathogenesis and treatment of multiple myeloma bone disease[J]. Chinese Journal of Clinicians(Electronic Edition), 2018, 12(11): 630-634.

多发性骨髓瘤(MM)是一种以浆细胞无限增殖扩散为主要表现的血液系统恶性肿瘤。多发性骨髓瘤骨病(MBD)是MM最为常见的并发症,超过70%的MM患者在疾病的进展过程中会出现骨损害,并且出现骨痛、溶骨性改变及病理性骨折等骨相关事件的增加。相关研究表明,MBD的发病机制与相关细胞因子及信号通路活性的改变有关,对相关细胞因子的研究也促进了一系列靶向治疗药物的研发。现就目前已知的参与MBD发病机制的重要细胞因子及相关临床靶向治疗进展进行综述。

Multiple myeloma (MM) is a hematological malignancy characterized by infinite proliferation and diffusion of plasma cells. Multiple myeloma bone disease (MBD) is the most common complication of MM. More than 70% of MM patients have bone damage in the course of disease progression, which leads to the increase of bone-related events such as bone pain, osteolytic changes, and pathological fractures. Relevant studies have shown that the pathogenesis of MBD is related to the changes of related cell factors and signaling pathways. The research on related cell factors has also promoted the development of a series of targeted therapeutic drugs. In this review, we summarize the important cell factors involved in the pathogenesis of MBD and the progress of it clinical targeted therapy.

1
Terpos E, Ntanasis-Stathopoulos I, Gavriatopoulou M, et al. Pathogenesis of bone disease in multiple myeloma: from bench to bedside [J]. Blood Cancer J, 2018, 8(1):7.
2
夏祖耀,杨惠娟,陈宝安. 多发性骨髓瘤骨病治疗研究进展[J]. 中国实验血液学杂志, 2016, 24(1):275-278.
3
Mundy GR, Raisz LG, Cooper RA, et al. Evidence for the secretion of an osteoclast stimulating factor in myeloma[J]. N Engl J Med, 1974, 291(20):1041-1046.
4
Hameed A, Brady JJ, Dowling P, et al. Bone disease in multiple myeloma: pathophysiology and management [J]. Cancer Growth Metastasis,2014, 7:33-42.
5
鲍立,黄晓军. 多发性骨髓瘤骨病患者骨代谢及调节因子水平及其意义[J]. 中华内科杂志, 2011, 50(3):243-247.
6
Seidel C, Hjertner Ø, Abildgaard N, et al. Serum osteoprotegerin levels are reduced in patients with multiple myeloma with lytic bone disease [J]. Blood, 2001, 98(7):2269-2271.
7
Jakob C,Goerke A,Terpos E, et al. Serum levels of total-RANKL in multiple myeloma [J]. Clin Lymphoma Myeloma, 2009, 9(6):430-435.
8
张娟,马艳萍. 多发性骨髓瘤骨病发病机制及靶向治疗的研究进展[J/CD]. 中华临床医师杂志(电子版), 2017, 11(6):1024-1028.
9
褚彬,陆敏秋,吴梦青, 等. 多发性骨髓瘤骨病临床特点及监测骨代谢标志物的临床意义[J]. 中华医学杂志, 2016, 96(18):1424-1429.
10
Fu J, Li S, Feng R, et al. Multiple myeloma-derived MMP-13 mediates osteoclast fusogenesis and osteolytic disease [J]. J Clin Invest, 2016, 126(5):1759-1772.
11
Baker J, Falconer AMD, Wilkinson DJ, et al. Protein kinase D3 modulates MMP1 and MMP13 expression in human chondrocytes [J]. PLoS One, 2018, 13(4):e0195864.
12
Salem AR, Korde N, Venzon DJ. Expression of the IL-6 receptor alpha-chain (CD126) in normal and abnormal plasma cells in monoclonal gammopathy of undetermined significance and smoldering myeloma [J]. Leuk Lymphoma, 2018, 59(1):178-186.
13
Piddock RE, Marlein CR, Abdul-Aziz A, et al. Myeloma-derived macrophage inhibitory factor regulates bone marrow stromal cell-derived IL-6 via c-MYC [J]. J Hematol Oncol, 2018, 11(1):66.
14
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 [J]. N Engl J Med, 2003, 349(26):2483-2494.
15
Giuliani N, Morandi F, Tagliaferri S, et al. Production of Wnt inhibitors by myeloma cells: potential effects on canonical Wnt pathway in the bone microenvironment [J]. Cancer Res, 2007, 67(16):7665-7674.
16
Liu Z, Liu H, Yuan X, et al. Downregulation of Pim-2 induces cell cycle arrest in the G0/G1 phase via the p53-non-dependent p21 signaling pathway [J]. Oncol Lett, 2018, 15(4):4079-4086.
17
Hiasa M, Teramachi J, Oda A, et al. Pim-2 kinase is an important target of treatment for tumor progression and bone loss in myeloma [J]. Leukemia, 2015, 29(1):207-217.
18
Taura A, Furuta K, Yamaguchi T, et al. Regulation of histamine synthesis and tryptase expression through transcription factors, growth factor independent 1 (Gfi1) and Gfi1b, in murine cultured mast cells [J]. Biol Pharm Bull, 2014, 37(1):81-86.
19
Harousseau JL, Moreau P. Autologous hematopoietic stem-cell transplantation for multiple myeloma [J]. N Engl J Med, 2009, 360(25):2645-2654.
20
Mir MA, Kapoor P, Kumar S, et al.Trends and outcomes in allogeneic hematopoietic stem cell transplant for multiplemyeloma at Mayo Clinic [J]. Clin Lymphoma Myeloma Leuk, 2015, 15(6):349-357.e2.
21
国际骨髓瘤基金会中国多发性骨髓瘤工作组外科治疗专家. 多发性骨髓瘤骨病外科治疗中国专家共识[J]. 中华骨科杂志, 2016, 36(4):193-199.
22
Matuschek C, Ochtrop TA, Lke E, et al. Effects of radiotherapy in the treatment of multiple myeloma: a retrospective analysis of a Single Institution [J]. Radiat Oncol, 2015, 10:71.
23
Raje N, Terpos E, Willenbacher W, et al. Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomised, controlled, phase 3 study [J]. Lancet Oncology, 2018, 19(3).
24
Raje N, Vadhan-Raj S, Willenbacher W, et al. Evaluating results from the multiple myeloma patient subset treated with denosumab or zoledronic acid in a randomized phase 3 trial [J]. Blood Cancer J, 2016, 6:e378.
25
Yee AJ, Raje NS. Denosumab for the treatment of bone disease in solid tumors and multiple myeloma [J]. Future Oncol, 2018, 14(3):195-203.
26
Fulciniti M, Tassone P, Hideshima T, et al. Anti-DKK1 mAb (BHQ880) as a potential therapeutic agent for multiple myeloma [J]. Blood, 2009, 114(2):371-379.
27
Rojas EA, Corchete LA, San-Segundo L, et al. Amiloride, an old diuretic drug, is a potential therapeutic agent for multiple myeloma [J]. Clin Cancer Res, 2017, 23(21):6602-6615.
28
Sher T, Gertz MA. Antibody based immunotherapy for multiple myeloma: it′s about time[J]. Leuk Lymphoma, 2016, 57(2):269-275.
29
侯健,李荣. 新型蛋白酶体抑制剂在多发性骨髓瘤治疗中的应用[J]. 中国肿瘤临床, 2018, 45(11):542-547.
30
夏正婷. BAFF/APRIL与血液肿瘤性疾病[J]. 中国肿瘤生物治疗杂志, 2017, 24(5):567-570.
31
李敏燕,周凡,刘景华, 等. 多发性骨髓瘤患者血清B淋巴细胞活化因子和增殖诱导配体水平的测定及临床意义[J/CD]. 中华临床医师杂志(电子版), 2013, 7(15):6998-7001.
32
Neri P, Kumar S, Fulciniti MT, et al. Neutralizing B-cell activating factor antibody improves survival and inhibits osteoclastogenesis in a severe combined immunodeficient human multiple myeloma model [J]. Clin Cancer Res, 2007, 13(19):5903-5909.
33
Raje N, Faber E, Richardson PG, et al. Phase 1 study of tabalumab, a human anti-B-cell activating factor antibody, and bortezomib in patients with relapsed/refractory multiple myeloma [J]. Clin Cancer Res, 2016, 22(23):5688-5695.
[1] 马敏榕, 李聪, 周勤. 宫颈癌治疗研究现状[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(05): 497-504.
[2] 林昌盛, 战军, 肖雪. 上皮性卵巢癌患者诊疗中基因检测及分子靶向药物治疗[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(05): 505-510.
[3] 王璐, 樊杨. 子宫内膜癌相关生物标志物研究现状[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(05): 511-516.
[4] 娄丽丽, 刘瀚旻. 儿童哮喘易感基因及表观遗传学研究现状[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(03): 249-255.
[5] 闫甲, 刘双池, 王政宇. 胆囊癌肿瘤标志物的研究和应用进展[J]. 中华普通外科学文献(电子版), 2023, 17(05): 391-394.
[6] 徐瑜杰, 赵国栋. 晚期胃癌治疗方法的研究进展和挑战[J]. 中华普外科手术学杂志(电子版), 2023, 17(04): 451-455.
[7] 王昆, 潘迪, 王庆, 江克华, 孙发. 机器人手术治疗膀胱副神经节瘤一例报告[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(03): 291-292.
[8] 邵浩仁, 郭佳. 铁死亡的分子机制及其在前列腺癌治疗中的研究进展[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(03): 294-298.
[9] 南方护骨联盟前列腺癌骨转移专家组. 前列腺癌骨转移诊疗专家共识(2023版)[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(03): 201-208.
[10] 魏小勇. 原发性肝癌转化治疗焦点问题探讨[J]. 中华肝脏外科手术学电子杂志, 2023, 12(06): 602-607.
[11] 吴晨瑞, 廖锐, 贺强, 潘龙, 黄平, 曹洪祥, 赵益, 王永琛, 黄俊杰, 孙睿锐. MDT模式下肝动脉灌注化疗联合免疫靶向治疗肝细胞癌多处转移一例[J]. 中华肝脏外科手术学电子杂志, 2023, 12(06): 713-716.
[12] 吴寅, 陈智琴, 高勇, 权明. Her-2阳性结直肠癌的诊治进展[J]. 中华结直肠疾病电子杂志, 2023, 12(05): 420-425.
[13] 唐凯, 刘正峰, 宋佳蔚, 卢秀珍. 角膜巩膜干凹斑的研究进展[J]. 中华眼科医学杂志(电子版), 2023, 13(04): 231-235.
[14] 张坤淇, 张睿, 徐佳, 康庆林. 漂浮膝损伤的诊治进展[J]. 中华老年骨科与康复电子杂志, 2023, 09(04): 252-256.
[15] 金刚, 李英真, 施维, 李博. 帕金森病在病理生理学中的研究进展[J]. 中华脑科疾病与康复杂志(电子版), 2023, 13(05): 315-319.
阅读次数
全文


摘要