中国组织工程研究

中国组织工程研究 ›› 2019, Vol. 23 ›› Issue (21): 3398-3403.doi: 10.3969/j.issn.2095-4344.1725

• 干细胞基础实验 basic experiments of stem cells • 上一篇    下一篇

慢性粒单核细胞白血病患者骨髓成纤维集落形成单位功能及意义

徐若豪1，2，李 超1，2，吴 萍2，李敏明2，邓程新2，耿素霞2，赖沛龙2，陆泽生2，翁建宇1，2，杜 欣1，2   

  1. 1华南理工大学医学院，广东省广州市 510006；2广东省人民医院血液科，广东省医学科学院，广东省广州市 510080
  • 修回日期:2019-02-20 出版日期:2019-07-28 发布日期:2019-07-28
  • 通讯作者: 杜欣，博士，主任医师，华南理工大学医学院，广东省广州市 510006；广东省人民医院血液科，广东省医学科学院，广东省广州市 510080
  • 作者简介:徐若豪，男，1992年生，河南省新乡市人，汉族，华南理工大学医学院在读硕士研究生，主要从事血液恶性疾病的微环境研究。
  • 基金资助:

    广东省科技重大专项(2017B020230004)，项目负责人：杜欣

Bone marrow colony forming units-fibroblast in patients with chronic myelomonocytic leukemia: functions and clinical significance

Xu Ruohao1, 2, Li Chao1, 2, Wu Ping2, Li Minming2, Deng Chengxin2, Geng Suxia2, Lai Peilong2, Lu Zesheng2, Weng Jianyu1, 2, Du Xin1, 2   

  1. 1Medical School of South China University of Technology, Guangzhou 510006, Guangdong Province, China; 2Department of Hematology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
  • Revised:2019-02-20 Online:2019-07-28 Published:2019-07-28
  • Contact: Du Xin, MD, Chief physician, Medical School of South China University of Technology, Guangzhou 510006, Guangdong Province, China; Department of Hematology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
  • About author:Xu Ruohao, Master candidate, Medical School of South China University of Technology, Guangzhou 510006, Guangdong Province, China; Department of Hematology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
  • Supported by:

    the Major Science and Technology Project of Guangdong Province, No. 2017B020230004 (to DX)

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摘要：

文章快速阅读：

 

文题释义：
成纤维集落形成单位(CFU-F)：代表了一组具有多向分化潜能的间充质干细胞，具有成骨、成脂、成软骨等多向分化的潜力。骨髓细胞形成CFU-F的数量与状态反映了骨髓基质微环境对造血、成骨、成脂分化的支持水平，可作为评估骨髓基质微环境的简易指标。
慢性粒单核细胞白血病(chronic myelomonocytic leukemia，CMML)：是一种髓系恶性肿瘤，兼有骨髓发育异常与肿瘤细胞克隆性增殖的表现。其发病机制仍不明确，异常的骨髓微环境可能参与到慢性粒单核细胞白血病的发病中。

 

摘要
背景：研究表明，异常的骨髓微环境可能参与慢性粒单核细胞白血病的发生，成纤维集落形成单位(colony forming unit-fibroblast，CFU-F)代表了一组具有多系分化潜能的间充质干细胞，其功能、数量状态具有评价骨髓基质微环境状态的意义。
目的：评估慢性粒单核细胞白血病患者骨髓间充质干细胞形成CFU-F的能力与成骨分化潜能，探讨CFU-F指标与患者外周血细胞计数、疾病表现型等指标的相关性。
方法：①收集广东省人民医院血液科收治、资料齐全的慢性粒单核细胞白血病患者15例与对照组志愿者10例，比较两组间骨髓形成CFU-F的功能与分化潜能；②分析慢性粒单核细胞白血病患者骨髓CFU-F数量与初诊时外周血细胞计数、临床表现型、骨髓原始细胞及患者基因突变的相关性。实验方案得到广东省人民医院(广东省医学科学院)伦理委员会批准，批件号：[2018]002号。  
结果与结论：①15例慢性粒单核细胞白血病患者CFU-F数量低于对照组(P=0.04)，其中67%(10/15)的慢性粒单核细胞白血病患者骨髓CFU-F数量显著降低(P=0.00)，33%(5/15)患者CFU-F水平接近对照组(P=0.14)；②全组慢性粒单核细胞白血病患者骨髓间充质干细胞成骨转录因子Osterix及RUNX2的表达量显著降低(P < 0.05)，成骨分化潜能显著下降(P=0.00)；③慢性粒单核细胞白血病患者CFU-F数量与初诊时外周血白细胞、中性粒细胞以及单核细胞计数呈负相关，与外周血小板计数呈正相关；④在CFU-F数量显著降低的10例患者中，90%(9/10)外周血白细胞计数均升高(≥13×109 L-1，P=0.01)，50%(5/10)患者携带有NRAS/KRAS基因位点突变。⑤结果表明：慢性粒单核细胞白血病患者骨髓间充质干细胞功能受损，形成的CFU-F数量降低，CFU-F数量与外周血细胞计数以及患者临床特征具有相关性，提示了CFU-F指标具有潜在的临床价值。


中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程
ORCID: 0000-0001-9961-2549(徐若豪)

关键词: 成纤维集落形成单位, 骨髓, 间充质干细胞, 慢性粒单核细胞白血病, KRAS基因, NRAS基因, 成骨分化, 外周血细胞计数, MPN-CMML型, MDS-CMML型, 骨髓微环境

Abstract:

BACKGROUND: Studies have shown that abnormal bone marrow microenvironment is involved in the development of chronic myelomonocytic leukemia. Colony forming unit-fibroblast represents a group of multipotent mesenchymal stromal cells that can reflect the bone marrow stromal microenvironment in terms of cell function and number.
OBJECTIVE: To investigate the abilities of bone marrow mesenchymal stromal cells to form colony forming units-fibroblast and to differentiate towards osteoblasts in patients with chronic myelomonocytic leukemia and to study the relationship between colony forming unit-fibroblast counts and clinic characteristics (peripheral blood cell count and clinical phenotype).
METHODS: (1) Fifteen newly diagnosed chronic myelomonocytic leukemia patients admitted to the Department of Hematology, Guangdong Provincial People’s Hospital, and 10 volunteers (control) were enrolled. Functions and osteogenic potential of colony forming units-fibroblast were compared between two groups. (2) There was a correlation analysis between colony forming unit-fibroblast counts and clinical characteristics (peripheral blood cell count, clinical phenotype, percentage of bone marrow blasts and gene mutations). The study protocol was approved by the ethics committee of Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences) with the approval No. [2018]002.
RESULTS AND CONCLUSION: (1) The number of colony forming units-fibroblast formed in the patients with chronic myelomonocytic leukemia decreased as compared with the control group (P=0.04). The 10 of 15 (67%) patients showed remarkable reduction in the colony forming unit-fibroblast counts (P=0.00), while the rest 5 (33%) patients exhibited normal colony forming unit-fibroblast levels (P=0.14). (2) Expression levels of Osterix and Runx2 in the bone marrow mesenchymal stem cells of patients with chronic myelomonocytic leukemia were significantly lower than those in the control group. There was a limited osteogenic potential in the bone marrow mesenchymal stem cells of patients with chronic myelomonocytic leukemia (P=0.00). (3) Colony forming unit-fibroblast counts of patients with chronic myelomonocytic leukemia were negatively related to peripheral white blood cells, neutrocytes and monocytes counts, and were positively related to peripheral platelet counts. (4) Nine out of 10 (90%) patients with reduced colony forming unit-fibroblast counts exhibited a higher white blood cell level (≥ 13×109/L) (P=0.01), and 5 out of 10 (50%) patients carried NRAS/KRAS mutations. Findings from this study show limited function of colony forming unit-fibroblast formation and osteogenic differentiation in bone marrow mesenchymal stem cells of patients with chronic myelomonocytic leukemia. Moreover, the number of colony forming units-fibroblast seems to be correlated to peripheral blood cell counts and clinical features, indicating underlying significances in the diagnosis and prognosis of chronic myelomonocytic leukemia.

Key words: colony forming unit-fibroblast, bone marrow, mesenchymal stem cells, chronic myelomonocytic leukemia, KRAS gene, NRAS gene, osteogenic differentiation, peripheral blood cell count, MPN-CMML type, MDS-CMML type, bone marrow microenvironment

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