Abstract
Myelodysplastic syndrome (MDS) is a stem cell tumor characterized by dysplastic features and ineffective hematopoiesis in the early phase and leukemic progression in the late phase. Speculating that differences in the expression of genes and microRNA (miRNA) in control and MDS-derived erythroid progenitors may cause ineffective erythropoiesis, we sorted common megakaryocyte-erythroid progenitors (MEPs) in bone marrow cells from three lower-risk MDS patients, and compared expression levels of genes and miRNA with those from controls. In apoptosis-related pathways, the expression of some pro-apoptotic genes, such as cell death-inducing DFFA-like effector A, caspase 5, and Fas ligand, was elevated in MDS-derived MEPs, while those of anti-apoptotic CD40 and tumor necrosis factor were lower. In hematopoiesis-regulating pathways, RUNX1 and ETV6 genes showed reduced expression. Expression profiling revealed that three and 35 miRNAs were significantly up- and down-regulated in MDS-derived MEPs. MIR9 exhibited robust expression in MEPs and CD71+GlyA+ erythroid cells derived from one of the three patients. Interestingly, overexpression of MIR9 inhibited the accumulation of hemoglobin in UT-7/GM cells. Some of these alterations in gene and miRNA expression may contribute to the pathogenesis of ineffective hematopoiesis in lower-risk MDS and provide molecular markers for sub-classification and making a prognosis.
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Acknowledgments
We thank Ms. A. Okada for her special technical assistance. This work was financially supported by Grants-in-Aid from the Ministries of Education, Culture, Sports, Science and Technology (17016068), and Health, Labour and Welfare, Japan, the Japanese Society for the Promotion of Science (20390275, 18591086, 50337391), and Seki Minato Award from Dokkyo Medical University School of Medicine.
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The authors declare that they have no conflict of interest.
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Maki, K., Sasaki, K., Nagata, Y. et al. Expressional changes of genes and miRNA in common megakaryocyte-erythroid progenitors from lower-risk myelodysplastic syndrome. Int J Hematol 100, 361–369 (2014). https://doi.org/10.1007/s12185-014-1639-2
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DOI: https://doi.org/10.1007/s12185-014-1639-2