Establishment of a humanized APL model via the transplantation of PML-RARA-transduced human common myeloid progenitors into immunodeficient mice.
Establishment of a humanized APL model via the transplantation of PML-RARA-transduced human common myeloid progenitors into immunodeficient mice.
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通过将 PML-RARA 转导的人类共同骨髓祖细胞移植到免疫缺陷小鼠体内，建立人源化 APL 模型。
DOI：
10.1371/journal.pone.0111082
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ando K
中科院分区：
文献类型：
--
作者：
Matsushita H;Yahata T;Sheng Y;Nakamura Y;Muguruma Y;Matsuzawa H;Tanaka M;Hayashi H;Sato T;Damdinsuren A;Onizuka M;Ito M;Miyachi H;Pandolfi PP;Ando K
癌症生物学的最新进展表明，许多恶性肿瘤具有等级系统，白血病干细胞（LSC）或白血病起始细胞（LIC）似乎是疾病进展的必需品。急性早幼粒细胞白血病（APL）是急性髓细胞白血病的一种亚型，其特征在于形成PML-RARα融合蛋白，导致异常早幼粒细胞的积聚。为了了解人类APL白血病发生的确切机制，我们建立了一个人源化的体内APL模型，包括逆转录病毒转导PML-RARA到来自人脐带血的CD 34+造血细胞中，并将这些细胞移植到免疫缺陷小鼠中。该白血病细胞与人类APL细胞相似，其细胞浆中含有大量的嗜天青异常颗粒，表达CD 13、CD 33和CD 117，但不表达HLA-DR和CD 34，基因表达分析结果与人类APL细胞同属一类，对全反式维甲酸敏感。如在人类APL中所见，诱导的APL细胞在第二受体中显示出低移植效率，这在使用分选的CD 34 −组分进行的移植中也表现出。为了分析APL发生和发展的机制，用PML-RARA转导分离的人脐带血。来自CD 34 +/CD 38+细胞的共同髓系祖细胞（CMP）发展APL。这些发现表明，CMP是APL中PML-RARA的靶向部分，而产生的CD 34 − APL细胞可能具有维持肿瘤的能力。
Recent advances in cancer biology have revealed that many malignancies possess a hierarchal system, and leukemic stem cells (LSC) or leukemia-initiating cells (LIC) appear to be obligatory for disease progression. Acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia characterized by the formation of a PML-RARα fusion protein, leads to the accumulation of abnormal promyelocytes. In order to understand the precise mechanisms involved in human APL leukemogenesis, we established a humanized in vivo APL model involving retroviral transduction of PML-RARA into CD34+ hematopoietic cells from human cord blood and transplantation of these cells into immunodeficient mice. The leukemia well recapitulated human APL, consisting of leukemic cells with abundant azurophilic abnormal granules in the cytoplasm, which expressed CD13, CD33 and CD117, but not HLA-DR and CD34, were clustered in the same category as human APL samples in the gene expression analysis, and demonstrated sensitivity to ATRA. As seen in human APL, the induced APL cells showed a low transplantation efficiency in the secondary recipients, which was also exhibited in the transplantations that were carried out using the sorted CD34− fraction. In order to analyze the mechanisms underlying APL initiation and development, fractionated human cord blood was transduced with PML-RARA. Common myeloid progenitors (CMP) from CD34+/CD38+ cells developed APL. These findings demonstrate that CMP are a target fraction for PML-RARA in APL, whereas the resultant CD34− APL cells may share the ability to maintain the tumor.
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DOI：
10.1073/pnas.94.10.5302
发表时间：
1997-05-13
影响因子：
11.1
作者：
He, LZ;Tribioli, C;Pandolfi, PP
通讯作者：
Pandolfi, PP
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：
2.6
作者：
Kawada, H;Ando, K;Hotta, T
通讯作者：
Hotta, T
影响因子：
20.3
作者：
Guibal, Florence C.;Alberich-Jorda, Meritxell;Tenen, Daniel G.
通讯作者：
Tenen, Daniel G.
DOI：
10.1073/pnas.94.20.10901
发表时间：
1997-09-30
影响因子：
11.1
作者：
Ferrucci, PF;Grignani, F;Pelicci, PG
通讯作者：
Pelicci, PG