Microfluidic Single-Cell Drug Screening: Toward Personalized Precision Therapy in Chronic Myeloid Leukemia

IF 5.4 2区 工程技术 Q1 BIOCHEMICAL RESEARCH METHODS
Lab on a Chip Pub Date : 2025-09-18 DOI:10.1039/d5lc00779h
Hwisu Jeon, Yukyung Park, Soo-Hyun Kim, Chang-Yeol Jung, Hongtae Kim, Eujin Um, Dong-Wook Kim, Taesung Kim
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引用次数: 0

Abstract

Chronic myeloid leukemia (CML) treatment employs several FDA-approved BCR::ABL1 tyrosine kinase inhibitors (TKIs) with distinct efficacy and side effects influenced by patient-specific factors. This study introduces a microfluidic cell culture array for the comparative analysis of six BCR::ABL1 TKIs, namely imatinib, nilotinib, bosutinib, ponatinib, dasatinib, and asciminib, using CML-related cell lines. The device provides a continuous, chemostat-like microfluidic environment that enables quantitative drug sensitivity scoring. The microchambers for cell culture notably offer advantages for single-cell imaging of suspension leukemia cells, which tend to aggregate in conventional culture platforms. This system supports the detailed characterization of cell viability across various TKI types and concentrations, yielding comprehensive mathematical metrics to assess relative drug efficacy. In this study, we compared drug responses in K562 and Ba/F3 BCR::ABL1 cell lines, including T315I mutant variant, and specifically demonstrated that Ba/F3 cells harboring the T315I mutation exhibit resistance to the first- and second-generation TKIs, responding only to ponatinib and asciminib. We further validated the device with a CML patient-derived bone marrow sample, requiring only minimal adjustments to the experimental conditions. The proposed microfluidic single-cell-based screening array could refine treatment regimens and advance personalized medicine in CML.
微流控单细胞药物筛选:迈向慢性髓性白血病个体化精准治疗
慢性髓性白血病(CML)治疗采用几种fda批准的BCR::ABL1酪氨酸激酶抑制剂(TKIs),其疗效和副作用受患者特异性因素的影响。本研究介绍了一种微流控细胞培养阵列,用于比较分析6种BCR::ABL1 TKIs,即伊马替尼、尼洛替尼、博舒替尼、波纳替尼、达沙替尼和阿西米尼,使用cml相关细胞系。该装置提供了一个连续的,类似于化学抑制剂的微流体环境,使定量药物敏感性评分成为可能。细胞培养的微室为悬浮白血病细胞的单细胞成像提供了明显的优势,悬浮白血病细胞往往聚集在传统的培养平台上。该系统支持在不同TKI类型和浓度下细胞活力的详细表征,产生全面的数学指标来评估相对药物功效。在这项研究中,我们比较了K562和Ba/F3 BCR::ABL1细胞系(包括T315I突变变体)的药物反应,并特别证明了含有T315I突变的Ba/F3细胞对第一代和第二代TKIs具有耐药性,仅对ponatinib和asciminib有反应。我们进一步用CML患者来源的骨髓样本验证了该装置,只需要对实验条件进行最小的调整。提出的基于微流控单细胞的筛选阵列可以改进治疗方案,推进CML的个性化治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Lab on a Chip
Lab on a Chip 工程技术-化学综合
CiteScore
11.10
自引率
8.20%
发文量
434
审稿时长
2.6 months
期刊介绍: Lab on a Chip is the premiere journal that publishes cutting-edge research in the field of miniaturization. By their very nature, microfluidic/nanofluidic/miniaturized systems are at the intersection of disciplines, spanning fundamental research to high-end application, which is reflected by the broad readership of the journal. Lab on a Chip publishes two types of papers on original research: full-length research papers and communications. Papers should demonstrate innovations, which can come from technical advancements or applications addressing pressing needs in globally important areas. The journal also publishes Comments, Reviews, and Perspectives.
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