Transplantation of a myelodysplastic syndrome by a long-term repopulating hematopoietic cell
Transplantation of a myelodysplastic syndrome by a long-term repopulating hematopoietic cell
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DOI：
10.1073/pnas.0804507105
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发表时间：
2008-09-16
影响因子：
11.1
通讯作者：
Aplan, Peter D.
中科院分区：
文献类型：
--
作者：
Chung, Yang Jo;Choi, Chul Won;Aplan, Peter D.
骨髓增生异常综合征（MDS）是一组以造血功能低下、发育异常和向急性髓性白血病（AML）转化为特征的恶性前血液病。虽然它是公认的，许多恶性肿瘤可以移植，有很少的证据表明，一个癌前疾病实体，如MDS或结肠息肉，可以移植，并随后在体内发生恶性转化。使用在造血组织中表达NUP 98-HOXD 13（NHD 13）转基因的小鼠，我们表明MDS可以移植到WT受体。MDS骨髓的接受者表现出MDS的所有关键特征，包括外周血细胞减少、发育异常和向AML的转化。即使当移植10倍过量的WT细胞时，NHD 13细胞在38周内也胜过WT细胞。有限稀释实验表明，可传播疾病的细胞的频率约为1/6，000 -1/16，000，MDS也可作为癌前状态转移到第二受体。初次移植受者向AML的转化通常延迟（移植后46-49周）;然而，10例二次移植受者中有6例发生AML。这些发现表明MDS起源于可移植的、癌前的、长期再增殖的MDS起始细胞。
The myelodysplastic syndromes (MDS) comprise a group of premalignant hematologic disorders characterized by ineffective hematopoiesis, dysplasia, and transformation to acute myeloid leukemia (AML). Although it is well established that many malignancies can be transplanted, there is little evidence to demonstrate that a premalignant disease entity, such as MDS or colonic polyps, can be transplanted and subsequently undergo malignant transformation in vivo. Using mice that express a NUP98-HOXD13 (NHD13) transgene in hematopoietic tissues, we show that a MDS can be transplanted to WT recipients. Recipients of the MDS bone marrow displayed all of the critical features of MDS, including peripheral blood cytopenias, dysplasia, and transformation to AML. Even when transplanted with a 10-fold excess of WT cells, the NHD13 cells outcompeted the WT cells over a 38-week period. Limiting-dilution experiments demonstrated that the frequency of the cell that could transmit the disease was approximate to 1/6,000-1/16,000 and that the MDS was also transferable to secondary recipients as a premalignant condition. Transformation to AML in primary transplant recipients was generally delayed (46-49 weeks after transplant); however, 6 of 10 secondary transplant recipients developed AML. These findings demonstrate that MDS originates in a transplantable, premalignant, long-term repopulating, MDS-initiating cell.