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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Transplantation of a myelodysplastic syndrome by a long-term repopulating hematopoietic cell
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Transplantation of a myelodysplastic syndrome by a long-term repopulating hematopoietic cell

机译：长期增生造血细胞移植骨髓增生异常综合症

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摘要

The myelodysplastic syndromes (MDS) comprise a group of prema-lignant hematologic disorders characterized by ineffective hemato-poiesis, 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 premalig-nant 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 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.
机译：骨髓增生异常综合症（MDS）包括一组以血细胞生成无效，发育不良和转化为急性髓性白血病（AML）为特征的病前血液系统疾病。尽管已经确定可以移植许多恶性肿瘤，但是几乎没有证据表明可以移植主要疾病实体，例如MDS或结肠息肉，然后在体内进行恶性转化。使用在造血组织中表达NUP98-HOXD13（NHD13）转基因的小鼠，我们显示MDS可以移植到WT受体。 MDS骨髓的接收者表现出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。即使在移植了10倍过量的WT细胞后，NHD13细胞在38周的时间内仍胜过WT细胞。极限稀释实验表明，可以传播疾病的细胞频率为1 / 6,000-1 / 16,000，并且MDS也可以作为恶性前病转移至继发接受者。通常将原发移植接受者向AML的转化推迟（移植后46-49周）。但是，每10位二次移植受者中有6位发生了AML。这些发现表明，MDS起源于可移植，恶变前，长期重新繁殖的MDS起始细胞。

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