Transplantation of a myelodysplastic syndrome by a long-term repopulating hematopoietic cell

Chung, Yang Jo, Choi, Chul Won, Slape, Christopher, Fry, Terry and Aplan, Peter D. (2008) Transplantation of a myelodysplastic syndrome by a long-term repopulating hematopoietic cell. Proceedings of the National Academy of Sciences, 105 37: 14088-14093. doi:10.1073/pnas.0804507105


Author Chung, Yang Jo
Choi, Chul Won
Slape, Christopher
Fry, Terry
Aplan, Peter D.
Title Transplantation of a myelodysplastic syndrome by a long-term repopulating hematopoietic cell
Journal name Proceedings of the National Academy of Sciences   Check publisher's open access policy
ISSN 0027-8424
1091-6490
Publication date 2008-09-16
Sub-type Article (original research)
DOI 10.1073/pnas.0804507105
Open Access Status Not yet assessed
Volume 105
Issue 37
Start page 14088
End page 14093
Total pages 6
Place of publication Washington, DC, United States
Publisher National Academy of Sciences
Language eng
Formatted abstract
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 ≈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.
Keyword Hematopoiesis
HOX gene
Leukemia
NUP98
Transplant
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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