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Blood, 15 October 2007, Vol. 110, No. 8, pp. 3005-3014.
Prepublished online as a Blood First Edition Paper on July 6, 2007September 20, 2007; DOI 10.1182/blood-2007-03-079368.
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Submitted March 12, 2007
Accepted June 27, 2007
The molecular signature of MDS stem cells supports a stem cell origin of 5q- myelodysplastic syndromes
Lars Nilsson, Patrik Eden, Eleonor Olsson, Robert Mansson, Ingbritt Astrand-Grundstrom, Bodil Strombeck, Kim Theilgaard-Monch, Kristina Anderson, Robert Hast, Eva Hellstrom-Lindberg, Jan Samuelsson, Gosta Bergh, Claus Nerlov, Bertil Johansson, Mikael Sigvardsson, Ake Borg, and Sten Eirik W. Jacobsen*
Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund, Sweden
Complex Systems Division, Department of Theoretical Physics, Lund University, Lund, Sweden
DNA Microarray Resource Center, Department of Oncology, Lund University, Lund, Sweden
Department of Clinical Genetics, Lund University, Lund, Sweden
Granulocyte Research Laboratory, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Hematology Center, Karolinska University Hospital, Stockholm, Sweden
Department of Medicine, Division of Hematology, Karolinska University Hospital (Huddinge), Stockholm, Sweden
Department of Medicine, South Hospital, Karolinska Institute, Stockholm, Sweden
Department of Medicine, Helsingborg Hospital, Helsingborg, Sweden
EMBL, Mouse Biology Unit, Via Ramarini 32, Monterotondo, Italy
* Corresponding author; email: sten.jacobsen{at}med.lu.se.
Global gene expression profiling of highly purified 5q deleted CD34+CD38-Thy1+ cells in 5q- myelodysplastic syndromes (MDS) 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.

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