急性髓系白血病干细胞源性巨噬样细胞生物学特性的研究

刘嘉; 杨超; 杨世杰; 张曦; 余时沧; 段江洁; 高蕾

doi:10.16016/j.1000-5404.201801120

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急性髓系白血病干细胞源性巨噬样细胞生物学特性的研究

基础医学 | 更新时间：2026-01-09

- 急性髓系白血病干细胞源性巨噬样细胞生物学特性的研究
- Biological characteristics of acute myeloid leukemia stem cells-derived macrophage-like cells
- 第三军医大学学报 2018年40卷第15期页码：1350-1356
- 作者机构：
  
  1.400037 重庆, 陆军军医大学(第三军医大学)第二附属医院全军血液病中心
  2.400038 重庆, 陆军军医大学(第三军医大学)第一附属医院全军病理学研究所
- 作者简介：
  
  [高蕾，E-mail:gaolei7765@163.com GAO Lei, E-mail:gaolei7765@163.com
- 基金信息：
  
  国家自然科学基金面上项目(81570131);国家自然科学基金面上项目(81370593);国家重点研发计划(2016YFA0202104)
- DOI：10.16016/j.1000-5404.201801120
  中图分类号： R73-354;R730.23;R733.71
- 收稿：2018-01-14，
  
  修回：2018-03-08，
  
  纸质出版：2018-08-15
- 稿件说明：
移动端阅览
刘嘉, 杨超, 杨世杰, 等. 急性髓系白血病干细胞源性巨噬样细胞生物学特性的研究[J]. 第三军医大学学报, 2018,40(15):1350-1356.

Jia LIU, Chao YANG, Shijie YANG, et al. Biological characteristics of acute myeloid leukemia stem cells-derived macrophage-like cells[J]. Journal of Third Military Medical University, 2018, 40(15): 1350-1356.
刘嘉, 杨超, 杨世杰, 等. 急性髓系白血病干细胞源性巨噬样细胞生物学特性的研究[J]. 第三军医大学学报, 2018,40(15):1350-1356. DOI： 10.16016/j.1000-5404.201801120.

Jia LIU, Chao YANG, Shijie YANG, et al. Biological characteristics of acute myeloid leukemia stem cells-derived macrophage-like cells[J]. Journal of Third Military Medical University, 2018, 40(15): 1350-1356. DOI： 10.16016/j.1000-5404.201801120.

摘要

目的

探讨急性髓系白血病干细胞（acute myeloid leukemia stem cells， AML LSCs）分化成AML LSCs源性巨噬样细胞的生物学现象、生物学特点及潜在的病理学意义。

方法

分选AML细胞系Kasumi-3中AML LSCs，在巨噬细胞条件培养基中培养14 d，从形态学、免疫表型、分泌细胞因子、吞噬功能等角度鉴定获得的贴壁细胞，明确AML LSCs源性巨噬样细胞的基本生物学特点。检测与AML LSCs源性巨噬样细胞共培养的Kasumi-3细胞表面耐药蛋白水平、胞内化疗药物浓度和对柔红霉素（DNR）的摄药量，初步评价AML LSCs源性巨噬样细胞促进白血病耐药的作用及可能机制。

结果

培养获得的AML LSCs源性巨噬样细胞呈多形性，以多角形和椭圆形贴壁细胞为主，透射电镜观察发现细胞呈椭圆形，胞浆丰富，有较多空泡；近胞核处高尔基体富集；包膜绒毛丰富且较长。AML LSCs源性巨噬样细胞特异性表达CD11b、CD163、CD206，分泌一定水平IL-10和IL-13。细菌吞噬实验证明其可吞噬大量呈绿色杆状荧光的

E.coli

菌，随着孵育时间的延长，吞噬数量逐渐增多。激光共聚焦显微镜观察发现与AML LSCs源性巨噬样细胞共培养的Kasumi-3细胞表面ABC转运蛋白表达明显强于对照组，DNR摄药量低于悬浮培养Kasumi-3细胞（54.75±4.28

93.84±3.93，

0.01），对DNR、阿霉素（ADM）、阿糖胞苷（Ara-C）和足叶乙甙（VP-16）均有一定的耐药性。

结论

AML LSCs在特定条件下可以分化成为AML LSCs源性巨噬样细胞，后者有类似巨噬细胞的生物学特性，参与白血病耐药的形成。

Abstract

Objective

To explore the biological phenomena and potential pathological significance of macrophage-like cells differentiated from acute myeloid leukemia stem cells (AML LSCs).

Methods

After AML LSCs were selected from AML cell line Kasumi-3

the cells were cultured for 14 d in the macrophage-conditioned medium. Then

the AML LSCs-derived macrophage-like cells were identified in morphology

immunophenotype

cytokines and phagocytosis

respectively to determine the biological characteristics of the cells. The level of ATP-binding cassette (ABC) transporter

the concentrations of intracellular chemotherapeutic drugs

and daunorubicin (DNR) dosage of Kasumi-3 cells after co-cultured with AML LSCs-derived macrophage-like cells were studied respectively for the role and possible mechanism of AML LSCs-derived macrophage-like cells in promotion of drug resistance.

Results

Most of AML LSCs-derived macrophage-like cells

in polygonal shape

were mainly polygonal and oval attached cells. Transmission electron mi

croscopy displayed that the cells were oval

with plenty of cytoplasm and more vacuoles; the Golgi bodies were accumulated near the nucleus

and the capsular villi were rich and long. The cells specifically expressed CD11b

CD163 and CD206

and secreted IL-10 and IL-13. Phagocytosis test showed that the cells could phagocytize a large amount of GFP

E.coli

in a time-dependent manner. After co-cultured with AML LSCs-derived macrophage-like cells

the Kasumi-3 cells expressed higher level of ABC protein

and presented lower DNR dosage (54.75±4.28

93.84±3.93

0.01 when compared with the Kasumi-3 cells in suspension cultivation) and certain drug resistances to DNR

adriamycin (ADM)

cytarabine (Ara-C) and etoposide (VP-16).

Conclusion

AML LSCs can be differentiated into AML LSCs-derived macrophage-like cells under specific conditions. The latter cells show macrophage-like biological properties and take part in the formation of leukemia resistance.

关键词

Keywords

references

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