Apoptosis-Related Gene Expression Profiling in Hematopoietic Cell Fractions of MDS Patients

• Published in: PloS one Vol. 11; no. 11; p. e0165582
• Main Authors: Langemeijer, Saskia Mc, Mariani, Niccolo, Knops, Ruth, Gilissen, Christian, Woestenenk, Rob, de Witte, Theo, Huls, Gerwin, van der Reijden, Bert A, Jansen, Joop H
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.11.2016; Public Library of Science (PLoS)
• Subjects: Analysis; Apoptosis; Apoptosis Regulatory Proteins - genetics; Autophagy; Biology and Life Sciences; Bone marrow; Cancer; Case-Control Studies; CD13 antigen; CD34 antigen; Cell death; Cells (biology); Cells, Cultured; Cluster analysis; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene families; Genes; Genetic aspects; Hematology; Hematopoietic stem cells; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - metabolism; Hemopoiesis; Humans; Immunology; Laboratories; Leukemia; Medicine; Medicine and Health Sciences; Myelodysplastic syndrome; Myelodysplastic syndromes; Myelodysplastic Syndromes - genetics; Myelodysplastic Syndromes - pathology; Overexpression; Patients; Progenitor cells; Proteins; Stem cells; Netherlands
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0165582

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.