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Involvement and functional impairment of the CD34(+)CD38(-)Thy-1(+) hematopoietic stem cell pool in myelodysplastic syndromes with trisomy 8.
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- Nilsson, Lars (författare)
- Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine
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- Åstrand-Grundström, Ingbritt (författare)
- Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine
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- Anderson, Kristina (författare)
- Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine
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Arvidsson, Ingrid (författare)
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Hokland, Peter (författare)
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- Bryder, David (författare)
- Lund University,Lunds universitet,Institutionen för laboratoriemedicin,Medicinska fakulteten,Department of Laboratory Medicine,Faculty of Medicine
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Kjeldsen, Lars (författare)
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- Johansson, Bertil (författare)
- Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine
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- Hellström-Lindberg, Eva (författare)
- Karolinska Institutet
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- Hast, Robert (författare)
- Karolinska Institutet
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- Jacobsen, Sten Eirik W (författare)
- Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine
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(creator_code:org_t)
- American Society of Hematology, 2002
- 2002
- Engelska.
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 100:1, s. 259-267
- Relaterad länk:
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http://www.ncbi.nlm.... (free)
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http://dx.doi.org/10... (free)
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https://ashpublicati...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Nyckelord
- 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
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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