title: Despite differential gene expression profiles pediatric MDS derived mesenchymal stromal cells display functionality in vitro.
abstract: Pediatric myelodysplastic syndrome (MDS) is a heterogeneous disease covering a spectrum ranging from aplasia (RCC) to myeloproliferation (RAEB(t)). In adult-type MDS there is increasing evidence for abnormal function of the bone-marrow microenvironment. Here, we extensively studied the mesenchymal stromal cells (MSCs) derived from children with MDS. MSCs were expanded from the bone-marrow of 17 MDS patients (RCC: n=10 and advanced MDS: n=7) and pediatric controls (n=10). No differences were observed with respect to phenotype, differentiation capacity, immunomodulatory capacity or hematopoietic support. mRNA expression analysis by Deep-SAGE revealed increased IL-6 expression in RCC- and RAEB(t)-MDS. RCC-MDS MSC expressed increased levels of DKK3, a protein associated with decreased apoptosis. RAEB(t)-MDS revealed increased CRLF1 and decreased DAPK1 expressions. This pattern has been associated with transformation in hematopoietic malignancies. Genes reported to be differentially expressed in adult MDS-MSC did not differ between MSC of pediatric MDS and controls. An altered mRNA expression profile, associated with cell survival and malignant transformation, of MSC derived from children with MDS strengthens the hypothesis that the micro-environment is of importance in this disease. Our data support the understanding that pediatric and adult MDS are two different diseases. Further evaluation of the pathways involved might reveal additional therapy targets.
authors: Department of Pediatrics, Section Immunology, Hematology/Oncology and Hematopoietic Stem Cell Transplantation, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: f.g.j.calkoen@lumc.nl.
authors: F G J
authors: FG
authors: Calkoen
authors: Department of Pediatrics, Section Immunology, Hematology/Oncology and Hematopoietic Stem Cell Transplantation, Leiden University Medical Center, Leiden, The Netherlands.
authors: C
authors: C
authors: Vervat
authors: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors: M
authors: M
authors: van Pel
authors: Dutch Childhood Oncology Group (DCOG), The Hague, The Netherlands.
authors: V
authors: V
authors: de Haas
authors: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors: L S
authors: LS
authors: Vijfhuizen
authors: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors: E
authors: E
authors: Eising
authors: Laboratory for Diagnostic Genome Analysis, Leiden University Medical Center, Leiden, The Netherlands.
authors: W G M
authors: WG
authors: Kroes
authors: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors: P A C
authors: PA
authors: 't Hoen
authors: Dutch Childhood Oncology Group (DCOG), The Hague, The Netherlands; Department of Pediatric Oncology/Hematology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
authors: M M
authors: MM
authors: van den Heuvel-Eibrink
authors: Department of Pediatrics, Section Immunology, Hematology/Oncology and Hematopoietic Stem Cell Transplantation, Leiden University Medical Center, Leiden, The Netherlands; Department of Hematology/Oncology and Hematopoietic Stem Cell Transplantation, Hospital for Sick Children, University of Toronto, Toronto, Canada.
authors: R M
authors: RM
authors: Egeler
authors: Department of Pediatrics, Section Immunology, Hematology/Oncology and Hematopoietic Stem Cell Transplantation, Leiden University Medical Center, Leiden, The Netherlands.
authors: M J D
authors: MJ
authors: van Tol
authors: Department of Pediatrics, Section Immunology, Hematology/Oncology and Hematopoietic Stem Cell Transplantation, Leiden University Medical Center, Leiden, The Netherlands.
authors: L M
authors: LM
authors: Ball
mesh_terms: D000293:Adolescent; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003582:Cytogenetics / Q000379:methods; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D059467:Transcriptome