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Characterization of Rare, Dormant, and Therapy-Resistant Cells in Acute Lymphoblastic Leukemia

机译：急性淋巴细胞白血病中罕见，休眠和抗治疗细胞的特征

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Tumor relapse is associated with dismal prognosis, but responsible biological principles remain incompletely understood. To isolate and characterize relapse-inducing cells, we used genetic engineering and proliferation-sensitive dyes in patient-derived xenografts of acute lymphoblastic leukemia (ALL). We identified a rare subpopulation that resembled relapse-inducing cells with combined properties of long-term dormancy, treatment resistance, and stemness. Single-cell and bulk expression profiling revealed their similarity to primary ALL cells isolated from pediatric and adult patients at minimal residual disease (MRD). Therapeutically adverse characteristics were reversible, as resistant, dormant cells became sensitive to treatment and started proliferating when dissociated from the in vivo environment. Our data suggest that ALL patients might profit from therapeutic strategies that release MRD cells from the niche.
机译：肿瘤复发与预后不良有关，但负责任的生物学原理仍未完全理解。为了分离和表征复发诱导细胞，我们在患者来源的急性淋巴细胞白血病（ALL）异种移植物中使用了基因工程和增殖敏感染料。我们确定了一种罕见的亚群，其类似于诱导复发的细胞，具有长期休眠，治疗抗性和干性的综合特性。单细胞和大量表达谱揭示了它们与从小儿和成年患者中分离到的原发性ALL细胞的相似性，而这些残余细胞具有最小残留疾病（MRD）。治疗上的不利特征是可逆的，因为耐药的休眠细胞对治疗敏感，并且在与体内环境分离时开始增殖。我们的数据表明，所有患者都可能会从利基释放MRD细胞的治疗策略中受益。

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