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

Jo Chung Yang, Won Choi Chul, Christopher Slape, Terry Fry, Peter D. Aplan

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)14088-14093
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number37
DOIs
Publication statusPublished - 2008 Sep 16

Keywords

  • HOX gene
  • Hematopoiesis
  • Leukemia
  • NUP98
  • Transplant

ASJC Scopus subject areas

  • General

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