Cytokines increase engraftment of human acute myeloid leukemia cells in immunocompromised mice but not engraftment of human myelodysplastic syndrome cells.
Cytokines increase engraftment of human acute myeloid leukemia cells in immunocompromised mice but not engraftment of human myelodysplastic syndrome cells.
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DOI：
10.3324/haematol.2017.183202
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发表时间：
2018-06
期刊：
影响因子：
10.1
通讯作者：
Carroll M
中科院分区：
文献类型：
--
作者：
Krevvata M;Shan X;Zhou C;Dos Santos C;Habineza Ndikuyeze G;Secreto A;Glover J;Trotman W;Brake-Silla G;Nunez-Cruz S;Wertheim G;Ra HJ;Griffiths E;Papachristou C;Danet-Desnoyers G;Carroll M
人类骨髓疾病（包括急性髓系白血病、骨髓增生异常综合征和骨髓增生性肿瘤）的患者来源异种移植模型对于临床前研究中疾病的生物学至关重要。然而，很少有研究将这些模型用于比较目的。先前的研究表明，急性髓系白血病原始细胞对人类造血细胞因子有反应，而骨髓增生异常综合征细胞则不会。我们将 NSG 小鼠中急性髓性白血病细胞和骨髓增生异常综合征细胞的植入情况与具有人类细胞因子转基因表达的 NSG-S 小鼠进行了比较。我们观察到，移植到 NSG 小鼠中的所有原发性急性髓系白血病样本 (n=77) 中只有 50% 提供了有用的植入水平（骨髓中 >0.5% 的人类母细胞）。相比之下，82% 的原发性急性髓系白血病样本移植到 NSG-S 小鼠中，白血病负担更高，生存期更短。此外，来自骨髓增生异常综合征患者的所有 5 个注射样本在第 6 周均显示出持续植入；然而，植入率大多较低（<2%），不会随着时间的推移而增加，并且仅受到使用 NSG-S 小鼠的短暂影响。间充质干细胞的共注射并没有增强人骨髓增生异常综合征细胞的植入。总体而言，我们得出的结论是，与骨髓增生异常综合征样本相比，急性髓系白血病样本的植入更加稳健，并且与骨髓增生异常综合征样本不同的是，急性髓系白血病细胞对人类细胞因子呈阳性反应，而骨髓增生异常综合征细胞则表现出对人类细胞因子的普遍无反应。
Patient-derived xenotransplantation models of human myeloid diseases including acute myeloid leukemia, myelodysplastic syndromes and myeloproliferative neoplasms are essential for studying the biology of the diseases in pre-clinical studies. However, few studies have used these models for comparative purposes. Previous work has shown that acute myeloid leukemia blasts respond to human hematopoietic cytokines whereas myelodysplastic syndrome cells do not. We compared the engraftment of acute myeloid leukemia cells and myelodysplastic syndrome cells in NSG mice to that in NSG-S mice, which have transgene expression of human cytokines. We observed that only 50% of all primary acute myeloid leukemia samples (n=77) transplanted in NSG mice provided useful levels of engraftment (>0.5% human blasts in bone marrow). In contrast, 82% of primary acute myeloid leukemia samples engrafted in NSG-S mice with higher leukemic burden and shortened survival. Additionally, all of 5 injected samples from patients with myelodysplastic syndrome showed persistent engraftment on week 6; however, engraftment was mostly low (<2%), did not increase over time, and was only transiently affected by the use of NSG-S mice. Co-injection of mesenchymal stem cells did not enhance human myelodysplastic syndrome cell engraftment. Overall, we conclude that engraftment of acute myeloid leukemia samples is more robust compared to that of myelodysplastic syndrome samples and unlike those, acute myeloid leukemia cells respond positively to human cytokines, whereas myelodysplastic syndrome cells demonstrate a general unresponsiveness to them.
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影响因子：
23.9
作者：
Medyouf, Hind;Mossner, Maximilian;Nowak, Daniel
通讯作者：
Nowak, Daniel
影响因子：
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作者：
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影响因子：
4
作者：
Kremer, Kimberly N.;Dudakovic, Amel;McGee-Lawrence, Meghan E.;Philips, Rachael L.;Hess, Allan D.;Smith, B. Douglas;van Wijnen, Andre J.;Karp, Judith E.;Kaufmann, Scott H.;Westendorf, Jennifer J.;Hedin, Karen E.
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Hedin, Karen E.
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DOI：
10.1016/s1470-2045(17)30416-3
发表时间：
2017-08
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Perl AE;Altman JK;Cortes J;Smith C;Litzow M;Baer MR;Claxton D;Erba HP;Gill S;Goldberg S;Jurcic JG;Larson RA;Liu C;Ritchie E;Schiller G;Spira AI;Strickland SA;Tibes R;Ustun C;Wang ES;Stuart R;Röllig C;Neubauer A;Martinelli G;Bahceci E;Levis M
通讯作者：
Levis M
影响因子：
23.9
作者：
Schepers, Koen;Pietras, Eric M.;Reynaud, Damien;Flach, Johanna;Binnewies, Mikhail;Garg, Trit;Wagers, Amy J.;Hsiao, Edward C.;Passegue, Emmanuelle
通讯作者：
Passegue, Emmanuelle