Characterization of Rare, Dormant, and Therapy-Resistant Cells in Acute Lymphoblastic Leukemia.
Characterization of Rare, Dormant, and Therapy-Resistant Cells in Acute Lymphoblastic Leukemia.
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DOI：
10.1016/j.ccell.2016.11.002
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发表时间：
2016-12-12
期刊：
影响因子：
50.3
通讯作者：
Jeremias I
中科院分区：
文献类型：
--
作者：
Ebinger S;Özdemir EZ;Ziegenhain C;Tiedt S;Castro Alves C;Grunert M;Dworzak M;Lutz C;Turati VA;Enver T;Horny HP;Sotlar K;Parekh S;Spiekermann K;Hiddemann W;Schepers A;Polzer B;Kirsch S;Hoffmann M;Knapp B;Hasenauer J;Pfeifer H;Panzer-Grümayer R;Enard W;Gires O;Jeremias I
肿瘤复发与预后不佳有关，但负责任的生物学原理仍不完全清楚。为了分离和表征复发诱导细胞，我们在急性淋巴细胞白血病（ALL）患者来源的异种移植物中使用了基因工程和增殖敏感染料。我们发现了一种罕见的亚群，类似于复发诱导细胞的长期休眠，治疗抗性和干性的组合属性。单细胞和批量表达谱显示，它们与从微小残留病（MRD）的儿童和成人患者中分离的原代ALL细胞相似。治疗不良特征是可逆的，因为耐药的休眠细胞对治疗变得敏感，并在与体内环境分离时开始增殖。我们的数据表明，ALL患者可能受益于从利基释放MRD细胞的治疗策略。在小鼠中生长的患者的ALL细胞含有罕见的不利亚群不利细胞显示治疗抗性、休眠和干细胞不利细胞模拟患者的原代细胞在最小残留疾病中从其环境中回收不利细胞使其对治疗敏感Ebinger et al.鉴定一种罕见的急性淋巴细胞白血病（ALL）细胞亚群，该细胞具有长期休眠、治疗抗性和白血病起始的综合特性。RNA测序结果显示，这些细胞与从微小残留病患者中分离的ALL细胞相似。
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. Patients' ALL cells growing in mice contain a rare unfavorable subpopulation Unfavorable cells display treatment resistance, dormancy, and stemness Unfavorable cells mimic patients' primary cells at minimal residual disease Retrieving unfavorable cells from their environment sensitizes them for treatment Ebinger et al. identify a rare subpopulation of acute lymphoblastic leukemia (ALL) cells that have the combined properties of long-term dormancy, treatment resistance, and leukemia initiation. RNA sequencing results show that these cells are similar to ALL cells isolated from patients at minimal residual disease.
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影响因子：
82.9
作者：
Gao, Hui;Korn, Joshua M.;Sellers, William R.
通讯作者：
Sellers, William R.
在儿童急性淋巴细胞白血病中，处于免疫表型成熟不同阶段的母细胞具有干细胞特性。
影响因子：
50.3
作者：
le Viseur C;Hotfilder M;Bomken S;Wilson K;Röttgers S;Schrauder A;Rosemann A;Irving J;Stam RW;Shultz LD;Harbott J;Jürgens H;Schrappe M;Pieters R;Vormoor J
通讯作者：
Vormoor J
影响因子：
82.9
作者：
Eppert, Kolja;Takenaka, Katsuto;Dick, John E.
通讯作者：
Dick, John E.
影响因子：
5.2
作者：
Graham, Susan M.;Vass, J. Keith;Graham, Gerard J.
通讯作者：
Graham, Gerard J.
影响因子：
4.2
作者：
Fehse, B;Uhde, A;Stockschlader, M
通讯作者：
Stockschlader, M