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 Astrand-Grundström; Bodil Strömbeck; Kim Theilgaard-Mönch; Kristina Anderson; Robert Hast; Eva Hellström-Lindberg; Jan Samuelsson; Gösta Bergh; Claus Nerlov; Bertil Johansson; Mikael Sigvardsson; Ake 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 Astrand-Grundström, Bodil Strömbeck, Kim Theilgaard-Mönch, Kristina Anderson, Robert Hast, Eva Hellström-Lindberg, Jan Samuelsson, Gösta Bergh, Claus Nerlov, Bertil Johansson, Mikael Sigvardsson, Ake Borg, Sten Eirik W Jacobsen

87 Citations (Scopus)

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
Journal	Blood
Volume	110
Issue number	8
Pages (from-to)	3005-14
Number of pages	9
ISSN	0006-4971
DOIs	https://doi.org/10.1182/blood-2007-03-079368
Publication status	Published - 2007
Externally published	Yes

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Nilsson, L., Edén, P., Olsson, E., Månsson, R., Astrand-Grundström, I., Strömbeck, B., Theilgaard-Mönch, K., Anderson, K., Hast, R., Hellström-Lindberg, E., Samuelsson, J., Bergh, G., Nerlov, C., Johansson, B., Sigvardsson, M., Borg, A., & Jacobsen, S. E. W. (2007). The molecular signature of MDS stem cells supports a stem-cell origin of 5q myelodysplastic syndromes. Blood, 110(8), 3005-14. https://doi.org/10.1182/blood-2007-03-079368

Nilsson, L, Edén, P, Olsson, E, Månsson, R, Astrand-Grundström, I, Strömbeck, B, Theilgaard-Mönch, K, Anderson, K, Hast, R, Hellström-Lindberg, E, Samuelsson, J, Bergh, G, Nerlov, C, Johansson, B, Sigvardsson, M, Borg, A & 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. 3005-14. https://doi.org/10.1182/blood-2007-03-079368

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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 Astrand-Grundstr{\"o}m and Bodil Str{\"o}mbeck and Kim Theilgaard-M{\"o}nch and Kristina Anderson and Robert Hast and Eva Hellstr{\"o}m-Lindberg and Jan Samuelsson and G{\"o}sta Bergh and Claus Nerlov and Bertil Johansson and Mikael Sigvardsson and Ake Borg and Jacobsen, {Sten Eirik W}",

note = "Keywords: Aged; Aged, 80 and over; Antigens, CD34; Antigens, CD38; Antigens, Thy-1; CCAAT-Enhancer-Binding Proteins; Cell Lineage; Chromosomes, Human, Pair 5; Female; Gene Expression; Gene Expression Profiling; Hematopoietic Stem Cells; Humans; Image Processing, Computer-Assisted; In Situ Hybridization, Fluorescence; Male; Middle Aged; Myelodysplastic Syndromes; Nuclear Proteins; Polymerase Chain Reaction; Proto-Oncogene Proteins; RNA; Repressor Proteins",

year = "2007",

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

language = "English",

volume = "110",

pages = "3005--14",

journal = "Blood",

issn = "0006-4971",

publisher = "American Society of Hematology",

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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 - Astrand-Grundström, Ingbritt

AU - Strömbeck, Bodil

AU - Theilgaard-Mönch, Kim

AU - Anderson, Kristina

AU - Hast, Robert

AU - Hellström-Lindberg, Eva

AU - Samuelsson, Jan

AU - Bergh, Gösta

AU - Nerlov, Claus

AU - Johansson, Bertil

AU - Sigvardsson, Mikael

AU - Borg, Ake

AU - Jacobsen, Sten Eirik W

N1 - Keywords: Aged; Aged, 80 and over; Antigens, CD34; Antigens, CD38; Antigens, Thy-1; CCAAT-Enhancer-Binding Proteins; Cell Lineage; Chromosomes, Human, Pair 5; Female; Gene Expression; Gene Expression Profiling; Hematopoietic Stem Cells; Humans; Image Processing, Computer-Assisted; In Situ Hybridization, Fluorescence; Male; Middle Aged; Myelodysplastic Syndromes; Nuclear Proteins; Polymerase Chain Reaction; Proto-Oncogene Proteins; RNA; Repressor Proteins

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 - Journal article

C2 - 17616640

SN - 0006-4971

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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