Ebinger Sarah, Özdemir Erbey Ziya, Ziegenhain Christoph, Tiedt Sebastian, Castro Alves Catarina, Grunert Michaela, Dworzak Michael, Lutz Christoph, Turati Virginia A, Enver Tariq, Horny Hans-Peter, Sotlar Karl, Parekh Swati, Spiekermann Karsten, Hiddemann Wolfgang, Schepers Aloys, Polzer Bernhard, Kirsch Stefan, Hoffmann Martin, Knapp Bettina, Hasenauer Jan, Pfeifer Heike, Panzer-Grümayer Renate, Enard Wolfgang, Gires Olivier, Jeremias Irmela
Department of Gene Vectors, Helmholtz Zentrum München, German Center for Environmental Health (HMGU), 81377 Munich, Germany.
Anthropology and Human Genomics, Department Biology II, Faculty of Biology, Ludwig-Maximilians-Universität München, 82152 Martinsried, Germany.
Cancer Cell. 2016 Dec 12;30(6):849-862. doi: 10.1016/j.ccell.2016.11.002. Epub 2016 Dec 1.
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.
肿瘤复发与预后不良相关，但其中的生物学原理仍未完全明了。为了分离并鉴定诱导复发的细胞，我们在急性淋巴细胞白血病（ALL）患者来源的异种移植模型中使用了基因工程技术和增殖敏感染料。我们鉴定出了一个罕见的亚群，其具有长期休眠、耐药性和干性等综合特性，类似于诱导复发的细胞。单细胞和整体表达谱分析显示，它们与从儿科和成年患者的微小残留病（MRD）中分离出的原发性ALL细胞相似。治疗上的不利特征是可逆的，因为耐药的休眠细胞在脱离体内环境后对治疗变得敏感并开始增殖。我们的数据表明，ALL患者可能会从将MRD细胞从其微环境中释放出来的治疗策略中获益。
