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 - 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 -
