Involvement and functional impairment of the CD34(+)CD38(-)Thy-1(+) hematopoietic stem cell pool in myelodysplastic syndromes with trisomy 8.
Author
Summary, in English
Clonality studies of mature cells suggest that the primary transformation event in myelodysplastic syndrome (MDS) most frequently occurs in a myeloid-restricted progenitor, a hypothesis supported by recent studies of purified CD34(+)Thy1(+) hematopoietic stem cells (HSCs) in cases with trisomy 8 (+8). In contrast, we recently demonstrated that a lymphomyeloid HSC is the target for transformation in MDS cases with del(5q), potentially reflecting heterogeneity within MDS. However, since +8 is known to frequently be a late event in the MDS transformation process, it remained a possibility that CD34(+)CD38(-)Thy1(+) HSC disomic for chromosome 8 might be part of the MDS clone. In the present studies, although a variable fraction of CD34(+)CD38(-)Thy1(+) cells were disomic for chromosome 8, they did not possess normal HSC activity in long-term cultures and nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice. Mixing experiments with normal CD34(+)CD38(-) cells suggested that this HSC deficiency was intrinsic and not mediated by indirect mechanisms. Furthermore, investigation of 4 MDS cases with combined del(5q) and +8 demonstrated that the +8 aberration was always secondary to del(5q). Whereas del(5q) invariably occurs in CD34(+)CD38(-)Thy-1(+) HSCs, the secondary +8 event might frequently arise in progeny of MDS HSCs. Thus, CD34(+)CD38(-)Thy1(+) HSCs are invariably part of the MDS clone also in +8 patients, and little HSC activity can be recovered from the CD34(+) CD38(-)Thy1(+) HSC. Finally, in advanced cases of MDS, the MDS reconstituting activity is exclusively derived from the minor CD34(+)CD38(-) HSC population, demonstrating that MDS stem cells have a similar phenotype as normal HSCs, potentially complicating the development of autologous transplantation for MDS.
Publishing year
2002
Language
English
Pages
259-267
Publication/Series
Blood
Volume
100
Issue
1
Links
Document type
Journal article
Publisher
American Society of Hematology
Topic
- Hematology
Keywords
- Male
- Human
- Hematopoietic Stem Cells : pathology
- Hematopoietic Stem Cells : immunology
- Female
- Clone Cells : pathology
- Clone Cells : immunology
- Pair 8
- Chromosomes
- Neoplastic : pathology
- Cell Transformation
- Neoplastic : genetics
- Thy-1 : analysis
- Antigens
- Differentiation : analysis
- CD34 : analysis
- 80 and over
- Aged
- Middle Age
- Myelodysplastic Syndromes : etiology
- Myelodysplastic Syndromes : genetics
- Myelodysplastic Syndromes : pathology
- NAD+ Nucleosidase : analysis
- Support
- Non-U.S. Gov't
- Trisomy
- Tumor Stem Cells : immunology
- Tumor Stem Cells : pathology
Status
Published
ISBN/ISSN/Other
- ISSN: 1528-0020