title: Apoptosis-Related Gene Expression Profiling in Hematopoietic Cell Fractions of MDS Patients.
abstract: Although the vast majority of patients with a myelodysplastic syndrome (MDS) suffer from cytopenias, the bone marrow is usually normocellular or hypercellular. Apoptosis of hematopoietic cells in the bone marrow has been implicated in this phenomenon. However, in MDS it remains only partially elucidated which genes are involved in this process and which hematopoietic cells are mainly affected. We employed sensitive real-time PCR technology to study 93 apoptosis-related genes and gene families in sorted immature CD34+ and the differentiating erythroid (CD71+) and monomyeloid (CD13/33+) bone marrow cells. Unsupervised cluster analysis of the expression signature readily distinguished the different cellular bone marrow fractions (CD34+, CD71+ and CD13/33+) from each other, but did not discriminate patients from healthy controls. When individual genes were regarded, several were found to be differentially expressed between patients and controls. Particularly, strong over-expression of BIK (BCL2-interacting killer) was observed in erythroid progenitor cells of low- and high-risk MDS patients (both p = 0.001) and TNFRSF4 (tumor necrosis factor receptor superfamily 4) was down-regulated in immature hematopoietic cells (p = 0.0023) of low-risk MDS patients compared to healthy bone marrow.
authors.affiliation: Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center (Radboudumc), Nijmegen, The Netherlands.|Department of Hematology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Saskia Mc
authors.initials: SM
authors.lastname: Langemeijer
authors.affiliation: Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center (Radboudumc), Nijmegen, The Netherlands.
authors.forename: Niccolo
authors.identifier: http://orcid.org/0000-0002-4986-2600
authors.initials: N
authors.lastname: Mariani
authors.affiliation: Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center (Radboudumc), Nijmegen, The Netherlands.
authors.forename: Ruth
authors.initials: R
authors.lastname: Knops
authors.affiliation: Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Christian
authors.initials: C
authors.lastname: Gilissen
authors.affiliation: Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center (Radboudumc), Nijmegen, The Netherlands.
authors.forename: Rob
authors.initials: R
authors.lastname: Woestenenk
authors.affiliation: Department of Tumor Immunology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Theo
authors.initials: T
authors.lastname: de Witte
authors.affiliation: Department of Hematology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.|Department of Hematology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Gerwin
authors.initials: G
authors.lastname: Huls
authors.affiliation: Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center (Radboudumc), Nijmegen, The Netherlands.
authors.forename: Bert A
authors.initials: BA
authors.lastname: van der Reijden
authors.affiliation: Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center (Radboudumc), Nijmegen, The Netherlands.
authors.forename: Joop H
authors.initials: JH
authors.lastname: Jansen
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000473:pathology
chemical_list: D051017:Apoptosis Regulatory Proteins