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The molecular signature of MDS stem cells supports a stem-cell origin of 5q - myelodysplastic syndromes

Nilsson, Lars LU ; Edén, Patrik LU ; Olsson, Eleonor LU ; Månsson, Robert LU ; Åstrand-Grundström, Ingbritt LU ; Strömbeck, Bodil LU ; Theilgaard-Moench, Kim LU ; Anderson, Kristina LU ; Hast, Robert and Hellström, Eva LU , et al. (2007) In Blood 110(8). p.3005-3014
Abstract
Global gene expression profiling of highly purified 5q-deleted CD34(+)CD38(-)Thy1(+) cells in 5q(-) myelodysplastic syndromes (MDSs) supported that they might originate from and outcompete normal CD34(+)CD38(-)Thy1(+) hematopoietic stem cells. Few but distinct differences in gene expression distinguished MDS and normal stem cells. Expression of BMI1, encoding a critical regulator of self-renewal, was up-regulated in 5q- stem cells. Whereas multiple previous MDS genetic screens failed to identify altered expression of the gene encoding the myeloid transcription factor CEBPA, stage-specific and extensive down-regulation of CEBPA was specifically observed in MDS progenitors. These studies establish the importance of molecular characterization... (More)
Global gene expression profiling of highly purified 5q-deleted CD34(+)CD38(-)Thy1(+) cells in 5q(-) myelodysplastic syndromes (MDSs) supported that they might originate from and outcompete normal CD34(+)CD38(-)Thy1(+) hematopoietic stem cells. Few but distinct differences in gene expression distinguished MDS and normal stem cells. Expression of BMI1, encoding a critical regulator of self-renewal, was up-regulated in 5q- stem cells. Whereas multiple previous MDS genetic screens failed to identify altered expression of the gene encoding the myeloid transcription factor CEBPA, stage-specific and extensive down-regulation of CEBPA was specifically observed in MDS progenitors. These studies establish the importance of molecular characterization of distinct stages of cancer stem and progenitor cells to enhance the resolution of stage-specific dysregulated gene expression. (Less)
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type
Contribution to journal
publication status
published
subject
in
Blood
volume
110
issue
8
pages
3005 - 3014
publisher
American Society of Hematology
external identifiers
  • wos:000250426700040
  • scopus:35548954717
ISSN
1528-0020
DOI
10.1182/blood-2007-03-079368
language
English
LU publication?
yes
id
a3a845e6-1463-4bd7-abbf-b95ef4eb4f09 (old id 653238)
date added to LUP
2007-12-14 08:47:45
date last changed
2017-10-29 03:31:12
@article{a3a845e6-1463-4bd7-abbf-b95ef4eb4f09,
  abstract     = {Global gene expression profiling of highly purified 5q-deleted CD34(+)CD38(-)Thy1(+) cells in 5q(-) myelodysplastic syndromes (MDSs) supported that they might originate from and outcompete normal CD34(+)CD38(-)Thy1(+) hematopoietic stem cells. Few but distinct differences in gene expression distinguished MDS and normal stem cells. Expression of BMI1, encoding a critical regulator of self-renewal, was up-regulated in 5q- stem cells. Whereas multiple previous MDS genetic screens failed to identify altered expression of the gene encoding the myeloid transcription factor CEBPA, stage-specific and extensive down-regulation of CEBPA was specifically observed in MDS progenitors. These studies establish the importance of molecular characterization of distinct stages of cancer stem and progenitor cells to enhance the resolution of stage-specific dysregulated gene expression.},
  author       = {Nilsson, Lars and Edén, Patrik and Olsson, Eleonor and Månsson, Robert and Åstrand-Grundström, Ingbritt and Strömbeck, Bodil and Theilgaard-Moench, Kim and Anderson, Kristina and Hast, Robert and Hellström, Eva and Samuelsson, Jan and Bergh, Goesta and Nerlov, Claus and Johansson, Bertil and Sigvardsson, Mikael and Borg, Åke and Jacobsen, Sten Eirik W},
  issn         = {1528-0020},
  language     = {eng},
  number       = {8},
  pages        = {3005--3014},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {The molecular signature of MDS stem cells supports a stem-cell origin of 5q - myelodysplastic syndromes},
  url          = {http://dx.doi.org/10.1182/blood-2007-03-079368},
  volume       = {110},
  year         = {2007},
}