Expressional changes of genes and miRNA in common megakaryocyte-erythroid progenitors from lower-risk myelodysplastic syndrome

• Published in: International journal of hematology Vol. 100; no. 4; pp. 361 - 369
• Main Authors: Maki, Kazuhiro, Sasaki, Ko, Nagata, Yasunobu, Nagasawa, Fusako, Nakamura, Yuka, Ogawa, Seishi, Mitani, Kinuko
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.10.2014; Springer; Springer Nature B.V
• Subjects: Aged; Biological and medical sciences; Biomarkers - metabolism; Female; Gene Expression Regulation; Hematologic and hematopoietic diseases; Hematology; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Medicine; Medicine & Public Health; Megakaryocyte-Erythroid Progenitor Cells - metabolism; Megakaryocyte-Erythroid Progenitor Cells - pathology; MicroRNAs - biosynthesis; Middle Aged; Myelodysplastic Syndromes - diagnosis; Myelodysplastic Syndromes - metabolism; Myelodysplastic Syndromes - pathology; Oncology; Original Article; Prognosis; microRNA; Megakaryocyte-erythroid progenitors; Ineffective hematopoiesis; Myelodysplastic syndrome; Erythropoiesis; RNA interference; Hematology; Stem cell; Micro RNA; Hematopoietic cell; Megakaryocyte; Malignant hemopathy; Gene silencing; Gene; Hematopoiesis; Risk factor; Genetics; Cancer
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-014-1639-2

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.