中国组织工程研究

中国组织工程研究 ›› 2010, Vol. 14 ›› Issue (1): 152-156.doi: 10.3969/j.issn.1673-8225.2010.01.032

• 干细胞综述 • 上一篇    下一篇

多发性骨髓瘤干细胞
表面标记和信号传导通路的作用与意义

鄢艳红，李惠民   

  1. 昆明医学院第一附属医院血液科，云南省昆明市 650032
  • 出版日期:2010-01-04 发布日期:2010-01-04
  • 通讯作者: 李惠民，昆明医学院第一附属医院血液科，云南省昆明市 650032
  • 作者简介:鄢艳红，女，1982年生，湖北省荆州市人，汉族，昆明医学院在读硕士，主要从事血液肿瘤方面的研究。 skyting724@tom.com
  • 基金资助:

    云南省自然科学基金面上项目(2006C0076M)

Multiple myeloma stem cells: Effect and significance of surface markers and signal transduction pathways

Yan Yan-hong, Li Hui-min   

  1. Department of Hematology, First Affiliated Hospital, Kunming Medical College, Kunming   650032, Yunnan Province, China
  • Online:2010-01-04 Published:2010-01-04
  • Contact: Li Hui-min, Department of Hematology, First Affiliated Hospital, Kunming Medical College, Kunming 650032, Yunnan Province, China
  • About author:Yan Yan-hong, Studying for master’s degree, Department of Hematology, First Affiliated Hospital, Kunming Medical College, Kunming 650032, Yunnan Province, China skyting724@tom.com
  • Supported by:

    the General Program of Natural Science Fountation of Yunnan Province, No. 2006C0076M*

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摘要：

背景：多发性骨髓瘤中存在一小部分比例的骨髓瘤干细胞，具有干细胞特性，有自我更新、无限增殖及多向分化的能力，是多发性骨髓瘤形成、进展、复发和耐药的根源。

目的：就多发性骨髓瘤干细胞生物学特性、免疫表型、分离与鉴定及针对该类细胞的信号传导通路和靶向治疗进行综述。

方法：应用计算机检索Medline数据库(1999-01/2009-04)，以mutiple myeloma stem cells，heterogeneity，phenotypic analysis，signaling pathways，target therapy为检索词；应用计算机检索CNKI数据库(1999-01/2009-04)、CBM数据库(1999-01/2009-04)，以多发性骨髓瘤干细胞、异质性、干细胞分离与鉴定、信号传导、靶向治疗为检索词。

结果与结论：共收集126篇关于多发性骨髓瘤干细胞相关的文献，中文30篇，英文96篇，排除发表较早、重复及类似研究，纳入30篇符合标准的文献。目前普遍认为多发性骨髓瘤干细胞可能源于正常干细胞的积累突变和通过基因突变重新获得自我更新能力的祖细胞或已经完全分化的成熟细胞。循环克隆记忆性B细胞具有自我更新和多向分化的潜能，代表了多发性骨髓瘤干细胞。多发性骨髓瘤干细胞特异标志物正处于研究阶段，目前主要采用SP细胞分选和醛脱氢酶活性检测分离骨髓瘤干细胞。多发性骨髓瘤干细胞通过hedgehog，wnt及notch等信号通路而具有自我更新的特性，当这些信号传导通路出现异常时，就导致了肿瘤的发生及肿瘤细胞的无控制性增长。针对肿瘤干细胞进行选择性靶向治疗是制定肿瘤治疗策略的一个新的重要方向，肿瘤干细胞特有的表面标记和信号传导通路可以作为杀伤肿瘤干细胞而控制肿瘤发展的靶点。

关键词: 多发性骨髓瘤, 骨髓瘤干细胞, 异质性, 信号传导, 靶向治疗

Abstract:

BACKGROUND: Cancer stem cell is a minority population of cancer cells in multiple myeloma possessing the properties of stem cells: self-renewal, multi-directional differentiation and long-term proliferation, which mediating disease initiation, relapse, progression and drug resistance.

OBJECTIVE: To review characteristics of biology, phenotypic analyses, sorting and identification in clonogenic myeloma cells, the signaling pathways with in myeloma stem cells and the target therapy related.

METHODS: Application of computer search Medline database (1999-01/2009-04), using “multiple myeloma stem cells, heterogeneity, phenotypic analysis, signaling pathways, target therapy” as key words; application of computer search CNKI database (1999-01/2009-04) and CBM Database (1999-01/2009-04) using “multiple myeloma stem cells, heterogeneity, stem cell separation and identification, signal transduction, targeted therapy as key words”.

RESULTS AND CONCLUSION: We collected for 126 literatures on the multiple myeloma stem cell-related, which include 30 Chinese articles and 96 English articles, excluding published earlier, repeated, and similar studies into 30 sub-standard literatures. Now widely recognized that multiple myeloma stem cells may be derived from normal stem cells, the accumulation of mutations and by gene mutation in regaining self-renewal capacity of progenitor cells or fully differentiated mature cells. Circulating clonotypic memory B-cell populations have self-renewal and multi-directional differentiation potential, which represent the cancer stem cells in multiple myeloma. The exact phenotype of multiple myeloma cancer stem cells has not been definitively established and researched remains. At present, both the side population cells and aldehyde dehydrogenase (ALDH) activity assays were mainly capable of isolating multiple myeloma cancer stem cells. Which to possess self-renewal ability by Hedgehog ,Wnt and Notch signaling pathways. When these signal transduction pathways appear abnormal, leading to the occurrence of the tumor and tumor cell growth in non-controlled. Against the cancer stem cell targeted therapy is a new and important direction of selective therapeutic strategies. Cancer stem cell specific surface markers and signal transduction pathways can be used as anti-cancer stem cells to control tumor development targets.

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