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.
authors.affiliation: Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Nilsson
authors.forename: Patrik
authors.initials: P
authors.lastname: Edén
authors.forename: Eleonor
authors.initials: E
authors.lastname: Olsson
authors.forename: Robert
authors.initials: R
authors.lastname: Månsson
authors.forename: Ingbritt
authors.initials: I
authors.lastname: Astrand-Grundström
authors.forename: Bodil
authors.initials: B
authors.lastname: Strömbeck
authors.forename: Kim
authors.initials: K
authors.lastname: Theilgaard-Mönch
authors.forename: Kristina
authors.initials: K
authors.lastname: Anderson
authors.forename: Robert
authors.initials: R
authors.lastname: Hast
authors.forename: Eva
authors.initials: E
authors.lastname: Hellström-Lindberg
authors.forename: Jan
authors.initials: J
authors.lastname: Samuelsson
authors.forename: Gösta
authors.initials: G
authors.lastname: Bergh
authors.forename: Claus
authors.initials: C
authors.lastname: Nerlov
authors.forename: Bertil
authors.initials: B
authors.lastname: Johansson
authors.forename: Mikael
authors.initials: M
authors.lastname: Sigvardsson
authors.forename: Ake
authors.initials: A
authors.lastname: Borg
authors.forename: Sten Eirik W
authors.initials: SE
authors.lastname: Jacobsen
mesh_terms: 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
chemical_list: 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