title: Genetic and epigenetic alterations of bone marrow stromal cells in myelodysplastic syndrome and acute myeloid leukemia patients.
abstract: We evaluated the characteristics of bone marrow stromal cells (BMSCs) and hematopoietic cells (HCs) from patients of myelodysplastic syndrome (MDS, n=21) and acute myeloid leukemia (AML, n=58), and compared the results with control BMSCs derived from healthy donors (n=8). The patient BMSCs had lower proliferative activity than that of the controls due to increased senescence. This retarded proliferation induced failure to obtain enough metaphase cells for karyotyping in patient BMSCs (10%). Patient BMSCs were genetically altered which was demonstrated by chromosome abnormalities in 5% of the patients (one MDS and three AML), whereas no clonal abnormalities were detected in the controls. The most common abnormality of the BMSCs was an extra chromosome 5, followed by an extra chromosome 7 and balanced translocations. The proportion of the abnormal metaphase cells was low (17.8%). We also analyzed the epigenetic changes of long interspersed nucleotide element 1 (LINE-1) repetitive element and CDKN2B using pyrosequencing. The quantitative measurement of global LINE-1 methylation demonstrated that patient BMSCs revealed global hypomethylation (68.2±3.8) compared with controls (72.9±3.4, P<0.001) and that the global hypomethylation of BMSCs were more significant in AML than in MDS patients (67.9±3.8, 69.4±4.2, respectively). These findings seem worthy of further evaluation of their association with ineffective hematopoiesis and leukemogenesis.
authors: Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Catholic Genetic Laboratory Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Yonggoo
authors: Y
authors: Kim
authors: Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Catholic Genetic Laboratory Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Dong Wook
authors: DW
authors: Jekarl
authors: Catholic Genetic Laboratory Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Jiyeon
authors: J
authors: Kim
authors: Catholic Genetic Laboratory Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Ahlm
authors: A
authors: Kwon
authors: Catholic Genetic Laboratory Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Hayoung
authors: H
authors: Choi
authors: Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Catholic Genetic Laboratory Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Seungok
authors: S
authors: Lee
authors: Department of Internal Medicine, Catholic Blood and Marrow Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Yoo-Jin
authors: YJ
authors: Kim
authors: Department of Internal Medicine, Catholic Blood and Marrow Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Hee-Je
authors: HJ
authors: Kim
authors: Department of Life Systems, Sookmyung Women's University, Seoul, Republic of Korea.
authors: Yonghwan
authors: Y
authors: Kim
authors: Catholic High-Performance Cell Therapy Center, Research Center for Stem Cell Therapeutics Evaluation, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Il-Hoan
authors: IH
authors: Oh
authors: Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Catholic Genetic Laboratory Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address: microkim@catholic.ac.kr.
authors: Myungshin
authors: M
authors: Kim
mesh_terms: D000328:Adult; D057890:Epigenomics; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000473:pathology / Q000502:physiology*; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000473:pathology*