The molecular signature of MDS stem cells supports a stem-cell origin of 5q myelodysplastic syndromes.
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.
Nilsson
Lars
L
Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund, Sweden.
Edén
Patrik
P
Olsson
Eleonor
E
Månsson
Robert
R
Astrand-Grundström
Ingbritt
I
Strömbeck
Bodil
B
Theilgaard-Mönch
Kim
K
Anderson
Kristina
K
Hast
Robert
R
Hellström-Lindberg
Eva
E
Samuelsson
Jan
J
Bergh
Gösta
G
Nerlov
Claus
C
Johansson
Bertil
B
Sigvardsson
Mikael
M
Borg
Ake
A
Jacobsen
Sten Eirik W
SE
D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins / Q000096:biosynthesis*; D019070:Cell Lineage / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D009687:Nuclear Proteins / Q000096:biosynthesis*; D063150:Polycomb Repressive Complex 1; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D012313:RNA / Q000032:analysis; D012097:Repressor Proteins / Q000096:biosynthesis*; D018800:Thy-1 Antigens / Q000378:metabolism
D018952:Antigens, CD34; C069077:BMI1 protein, human; D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D018800:Thy-1 Antigens; D012313:RNA; D063150:Polycomb Repressive Complex 1; D051997:ADP-ribosyl Cyclase 1