Acute myeloid leukemia cells are protected from spontaneous and drug-induced apoptosis by direct contact with a human bone marrow stromal cell line (HS-5)
Acute myeloid leukemia cells are protected from spontaneous and drug-induced apoptosis by direct contact with a human bone marrow stromal cell line (HS-5)
复制标题
DOI：
10.1016/s0301-472x(01)00612-9
复制
发表时间：
2001-04-01
影响因子：
2.6
通讯作者：
Banker, DE
中科院分区：
文献类型：
--
作者：
Garrido, SM;Appelbaum, FR;Banker, DE
Objective.我们研究了HS-5人骨髓基质细胞系对培养的原代白血病细胞存活和化疗敏感性的影响。将来自未经治疗的急性髓性白血病（AML）患者的总共30个骨髓（BM）样品与血清和生长因子一起培养96小时，不使用HS-5，或与HS-5单层直接接触，或通过transwell插入物与AML细胞分离的Kith HS-5。在一些实验中，在培养的最后18小时加入阿糖胞苷或道诺霉素。流式细胞术检测细胞凋亡率、bcl-2蛋白表达、增殖细胞核抗原表达和细胞周期分布。结果：与对照组相比，HS-5直接作用可显著抑制培养诱导和药物诱导的AML细胞凋亡。ARIL细胞与HS-5的直接接触显著增加了原代AML细胞的短期增殖和活力以及集落形成。HS-5介导的凋亡抑制与AML细胞中bcl-2蛋白的增加并不一致。非接触条件对药物诱导的细胞凋亡的抑制作用显著低于直接接触HS-5。AML细胞在HS-5单层上的共培养改善了体外白血病细胞存活率并减弱了化疗诱导的白血病细胞杀伤。这具有实际意义，增加了可以在体外分析的原发性AML样品的分数，并允许在更类似于骨髓微环境的生长条件下进行药物敏感性测试。(C)2001年国际实验血液学学会。爱思唯尔科学公司出版
Objective. In vitro culture systems that parallel in vivo growth conditions are needed to study leukemia biology and to accurately test therapeutic efficacies, We investigated the effects of the HS-5 human bone marrow stromal cell line on cultured primary leukemia cell survival and chemosensitivity.Materials and Methods. A total of 30 bone marrow (BM) samples from untreated acute myeloid leukemia (AML) patients were cultured for 96 hours with serum and growth factors, without HS-5, or in direct contact with HS-5 monolayers, or Kith HS-5 separated from AML, cells by transwell inserts. In some experiments, cytosine arabinoside or daunomycin was added for the last 18 hours of culture. Apoptosis frequencies, bcl-2 protein expression, proliferating cell nuclear antigen expression, and cell cycle distributions were determined in four-color flow cytometry analyses of CD45(+) leukemia cells,Results, In comparison to control growth conditions, direct contact with HS-5 significantly inhibited culture-induced and drug-induced apoptosis of AML cells. Direct contact of ARIL cells with HS-5 significantly increased short-term proliferation and viability, and colony formation of primary AML cells. HS-5-mediated apoptosis inhibition was not consistently associated with increased bcl-2 protein in AML cells. Noncontact conditions inhibited drug-induced apoptosis significantly less than direct contact with HS-5.Conclusion. Coculture of AML cells on HS-5 monolayers improved in vitro leukemia cell survival and attenuated chemotherapy-induced leukemia cell killing. This has practical significance, increasing the fraction of primary AML samples that can be analyzed in vitro, and allows drug sensitivity testing in growth conditions more similar to the bone marrow microenvironment. (C) 2001 International Society for Experimental Hematology. Published by Elsevier Science Inc.