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

Lars Nilsson; Patrik Edén; Eleonor Olsson; Robert Månsson; Ingbritt Åstrand-Grundström; Bodil Strömbeck; Kim Theilgaard-Moench; Kristina Anderson; Robert Hast; Eva Hellström; Jan Samuelsson; Goesta Bergh; Claus Nerlov; Bertil Johansson; Mikael Sigvardsson; Åke Borg; Sten Eirik W Jacobsen

doi:10.1182/blood-2007-03-079368

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

Lars Nilsson, Patrik Edén, Eleonor Olsson, Robert Månsson, Ingbritt Åstrand-Grundström, Bodil Strömbeck, Kim Theilgaard-Moench, Kristina Anderson, Robert Hast, Eva Hellström, Jan Samuelsson, Goesta Bergh, Claus Nerlov, Bertil Johansson, Mikael Sigvardsson, Åke Borg, Sten Eirik W Jacobsen

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	3005-3014
Journal	Blood
Volume	110
Issue number	8
DOIs	https://doi.org/10.1182/blood-2007-03-079368
Publication status	Published - 2007

Subject classification (UKÄ)

Hematology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1182/blood-2007-03-079368

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Nilsson, L., Edén, P., Olsson, E., Månsson, R., Åstrand-Grundström, I., Strömbeck, B., Theilgaard-Moench, K., Anderson, K., Hast, R., Hellström, E., Samuelsson, J., Bergh, G., Nerlov, C., Johansson, B., Sigvardsson, M., Borg, Å., & Jacobsen, S. E. W. (2007). The molecular signature of MDS stem cells supports a stem-cell origin of 5q - myelodysplastic syndromes. Blood, 110(8), 3005-3014. https://doi.org/10.1182/blood-2007-03-079368

@article{a3a845e614634bd7abbfb95ef4eb4f09,

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

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 = "Lars Nilsson and Patrik Ed{\'e}n and Eleonor Olsson and Robert M{\aa}nsson and Ingbritt {\AA}strand-Grundstr{\"o}m and Bodil Str{\"o}mbeck and Kim Theilgaard-Moench and Kristina Anderson and Robert Hast and Eva Hellstr{\"o}m and Jan Samuelsson and Goesta Bergh and Claus Nerlov and Bertil Johansson and Mikael Sigvardsson and {\AA}ke Borg and Jacobsen, {Sten Eirik W}",

year = "2007",

doi = "10.1182/blood-2007-03-079368",

language = "English",

volume = "110",

pages = "3005--3014",

journal = "Blood",

issn = "1528-0020",

publisher = "American Society of Hematology",

number = "8",

}

Nilsson, L, Edén, P, Olsson, E, Månsson, R, Åstrand-Grundström, I, Strömbeck, B, Theilgaard-Moench, K, Anderson, K, Hast, R, Hellström, E, Samuelsson, J, Bergh, G, Nerlov, C, Johansson, B , Sigvardsson, M , Borg, Å & Jacobsen, SEW 2007, 'The molecular signature of MDS stem cells supports a stem-cell origin of 5q - myelodysplastic syndromes', Blood, vol. 110, no. 8, pp. 3005-3014. https://doi.org/10.1182/blood-2007-03-079368

TY - JOUR

T1 - The molecular signature of MDS stem cells supports a stem-cell origin of 5q - myelodysplastic syndromes

AU - Nilsson, Lars

AU - Edén, Patrik

AU - Olsson, Eleonor

AU - Månsson, Robert

AU - Åstrand-Grundström, Ingbritt

AU - Strömbeck, Bodil

AU - Theilgaard-Moench, Kim

AU - Anderson, Kristina

AU - Hast, Robert

AU - Hellström, Eva

AU - Samuelsson, Jan

AU - Bergh, Goesta

AU - Nerlov, Claus

AU - Johansson, Bertil

AU - Sigvardsson, Mikael

AU - Borg, Åke

AU - Jacobsen, Sten Eirik W

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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.

U2 - 10.1182/blood-2007-03-079368

DO - 10.1182/blood-2007-03-079368

M3 - Article

SN - 1528-0020

VL - 110

SP - 3005

EP - 3014

JO - Blood

JF - Blood

IS - 8

ER -

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

Abstract

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UN SDGs

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