Transfer of multidrug resistance among acute myeloid leukemia cells via extracellular vesicles and their microRNA cargo
Transfer of multidrug resistance among acute myeloid leukemia cells via extracellular vesicles and their microRNA cargo
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DOI：
10.1016/j.leukres.2017.09.014
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发表时间：
2017-11-01
影响因子：
2.7
通讯作者：
Dogne, Jean-Michel
中科院分区：
文献类型：
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作者：
Bouvy, Celine;Wannez, Adeline;Dogne, Jean-Michel
急性白血病的治疗仍然具有挑战性，部分原因是耐药性和复发的发生。这种化疗耐药性是通过癌细胞耐药变体的克隆选择而建立的。最近，有人提出癌细胞之间的化疗耐药性通过细胞外囊泡（EV）进行水平转移。本研究的目的是探讨细胞外囊泡（EV）在急性髓系白血病化疗耐药中的作用。为此，我们对早幼粒细胞白血病 HL60 细胞系的敏感菌株及其多重耐药菌株 HL60/ AR 进行了研究，该菌株过度表达多重耐药蛋白 1 (MRP-1)。通过用 HL60/ AR 产生的 EV 处理 HL60 细胞，建立了两种菌株之间的化学抗性转移。这项研究表明，来自 HL60/AR 的 EV 可以与 HL60 细胞相互作用，并至少部分转移其化疗耐药性。 EV 处理的细胞开始表达 MRP-1，可能是由于 EV 运输的 MRP-1 和核酸的直接转移。在这种情况下，两种 microRNA 因其在与敏感或化疗耐药细胞相关的 EV 中的高差异表达而受到关注：miR-19b 和 miR-20a。由于循环 microRNA 存在于所有生物体液中，因此这些结果显示了它们作为急性髓系白血病化疗耐药生物标志物的潜在临床用途。
The treatment of acute leukemia is still challenging due in part to the development of resistance and relapse. This chemotherapeutics resistance is established by clonal selection of resistant variants of the cancer cells. Recently, a horizontal transfer of chemo-resistance among cancer cells via extracellular vesicles (EVs) has been suggested.The aim of this research was to investigate the role of EVs in chemo-resistance in acute myeloid leukemia. For this purpose, the sensitive strain of the promyelocytic leukemia HL60 cell line was studied along with its multiresistant strain, HL60/ AR that overexpresses the multidrug resistance protein 1 (MRP-1). A chemo-resistance transfer between the two strains was established by treating HL60 cells with EVs generated by HL60/ AR. This study reveals that EVs from HL60/ AR can interact with HL60 cells and transfer at least partially, their chemoresistance. EVs-treated cells begin to express MRP-1 probably due to a direct transfer of MRP-1 and nucleic acids transported by EVs. In this context, two microRNAs were highlighted for their high differential expression in EVs related to sensitive or chemo-resistant cells: miR-19b and miR-20a. Because circulating microRNAs are found in all biological fluids, these results bring out their potential clinical use as chemo-resistance biomarkers in acute myeloid leukemia.