An improved pre-clinical patient-derived liquid xenograft mouse model for acute myeloid leukemia.
An improved pre-clinical patient-derived liquid xenograft mouse model for acute myeloid leukemia.
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DOI：
10.1186/s13045-017-0532-x
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发表时间：
2017-10-06
影响因子：
28.5
通讯作者：
Chen Q
中科院分区：
文献类型：
--
作者：
Her Z;Yong KSM;Paramasivam K;Tan WWS;Chan XY;Tan SY;Liu M;Fan Y;Linn YC;Hui KM;Surana U;Chen Q
将患者来源的 AML（急性髓性白血病）细胞异种移植到 NOD-scid Il2rγ null (NSG) 小鼠中是评估这种人类血液恶性肿瘤的首选方法。然而，现有的在成年或新生NSG小鼠中静脉注射构建的模型存在植入效率差、外周血植入差或难以构建的问题。在这里，我们描述了一种改进的 AML 异种移植模型，其中将原代人 AML 细胞注射到 NSG 新生幼崽的肝内。引入来自 AML 患者的原代细胞导致受体小鼠的外周血、脾脏和骨髓 (BM) 中高水平的植入。移植的 AML 细胞的表型在连续移植过程中保持不变。这些小鼠出现了与人类 AML 一致的特征，包括脾脏肿大和 AML 细胞浸润到多个器官。重要的是，我们证明虽然白血病干细胞活性由CD34+CD117+亚群富集和介导，但CD34+CD117−亚群可以通过去分化获得CD34+CD117+表型。最后，我们评估了索拉非尼和瑞戈非尼在此 AML 模型中的治疗潜力，发现外周和脾脏 AML 细胞对这些治疗敏感，而 BM 为 AML 提供了保护环境。总的来说，我们改进的模型对于临床前 AML 研究来说是稳健的、易于构建且可靠的。本文的在线版本 (10.1186/s13045-017-0532-x) 包含补充材料，可供授权用户使用。
Xenotransplantation of patient-derived AML (acute myeloid leukemia) cells in NOD-scid Il2rγ null (NSG) mice is the method of choice for evaluating this human hematologic malignancy. However, existing models constructed using intravenous injection in adult or newborn NSG mice have inferior engraftment efficiency, poor peripheral blood engraftment, or are difficult to construct. Here, we describe an improved AML xenograft model where primary human AML cells were injected into NSG newborn pups intrahepatically. Introduction of primary cells from AML patients resulted in high levels of engraftment in peripheral blood, spleen, and bone marrow (BM) of recipient mice. The phenotype of engrafted AML cells remained unaltered during serial transplantation. The mice developed features that are consistent with human AML including spleen enlargement and infiltration of AML cells into multiple organs. Importantly, we demonstrated that although leukemic stem cell activity is enriched and mediated by CD34+CD117+ subpopulation, CD34+CD117− subpopulation can acquire CD34+CD117+ phenotype through de-differentiation. Lastly, we evaluated the therapeutic potential of Sorafenib and Regorafenib in this AML model and found that periphery and spleen AML cells are sensitive to these treatments, whereas BM provides a protective environment to AML. Collectively, our improved model is robust, easy-to-construct, and reliable for pre-clinical AML studies. The online version of this article (10.1186/s13045-017-0532-x) contains supplementary material, which is available to authorized users.
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去分化对干细胞驱动癌症突变获取时间的时间的影响。
影响因子：
4.3
作者：
Jilkine A;Gutenkunst RN
通讯作者：
Gutenkunst RN
影响因子：
82.9
作者：
Li S;Garrett-Bakelman FE;Chung SS;Sanders MA;Hricik T;Rapaport F;Patel J;Dillon R;Vijay P;Brown AL;Perl AE;Cannon J;Bullinger L;Luger S;Becker M;Lewis ID;To LB;Delwel R;Löwenberg B;Döhner H;Döhner K;Guzman ML;Hassane DC;Roboz GJ;Grimwade D;Valk PJ;D'Andrea RJ;Carroll M;Park CY;Neuberg D;Levine R;Melnick AM;Mason CE
通讯作者：
Mason CE
DOI：
10.1016/s0140-6736(12)61857-1
发表时间：
2013-01-26
期刊：
Lancet (London, England)
影响因子：
--
作者：
Demetri GD;Reichardt P;Kang YK;Blay JY;Rutkowski P;Gelderblom H;Hohenberger P;Leahy M;von Mehren M;Joensuu H;Badalamenti G;Blackstein M;Le Cesne A;Schöffski P;Maki RG;Bauer S;Nguyen BB;Xu J;Nishida T;Chung J;Kappeler C;Kuss I;Laurent D;Casali PG;GRID study investigators
通讯作者：
GRID study investigators
影响因子：
20.3
作者：
Ailles, LE;Gerhard, B;Hogge, DE
通讯作者：
Hogge, DE
影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Ward, Elizabeth
通讯作者：
Ward, Elizabeth