دورية أكاديمية
أعرض في EDS

The Effects of Human BDH2 on the Cell Cycle, Differentiation, and Apoptosis and Associations with Leukemia Transformation in Myelodysplastic Syndrome

التفاصيل البيبلوغرافية
العنوان: The Effects of Human BDH2 on the Cell Cycle, Differentiation, and Apoptosis and Associations with Leukemia Transformation in Myelodysplastic Syndrome
المؤلفون: Wen-Chi Yang, Sheng-Fung Lin, Shu-Chen Wang, Wan-Chi Tsai, Chun-Chieh Wu, Shih-Chi Wu
المصدر: International Journal of Molecular Sciences, Vol 21, Iss 9, p 3033 (2020)
بيانات النشر: MDPI AG, 2020.
سنة النشر: 2020
المجموعة: LCC:Biology (General)
LCC:Chemistry
مصطلحات موضوعية: acute leukemia, BDH2, LCN2, myelodysplastic syndrome (MDS), iron metabolism, Biology (General), QH301-705.5, Chemistry, QD1-999
الوصف: Iron overload is related to leukemia transformation in myelodysplastic syndrome (MDS) patients. Siderophores help to transport iron. Type 2-hydroxybutyrate dehydrogenase (BDH2) is a rate-limiting factor in the biogenesis of siderophores. Using qRT-PCR, we analyze BDH2mRNA expression in the bone marrow (BM) of 187 MDS patients, 119 de novo acute myeloid leukemia (AML) patients, and 43 lymphoma patients with normal BM. Elevated BDH2mRNA expression in BM is observed in MDS patients (n = 187 vs. 43, normal BM; P = 0.009), and this is related to ferritin levels. Patients with higher BDH2 expression show a greater risk of leukemia progression (15.25% vs. 3.77%, lower expression; P = 0.017) and shorter leukemia-free-survival (medium LFS, 9 years vs. 7 years; P = 0.024), as do patients with a ferritin level ≥350 ng/mL. Additionally, we investigate the mechanisms related to the prognostic ability of BDH2 by using BDH2-KD THP1. The cell cycle analysis, surface markers, and special stain studies indicate that BDH2-KD induces differentiation and decreases the growth rate of THP1 cells, which is associated with the retardation of the cell cycle. Moreover, many genes, including genes related to mitochondrial catabolism, oncogenes, tumor suppressor genes, and genes related to cell differentiation and proliferation influence BDH2-KD THP1 cells. Herein, we demonstrate that BDH2 is involved in cell cycle arrest and the inhibition of differentiation in malignant cells. Furthermore, the high BDH2 expression in MDS patients could be suggestive of a poor prognostic factor. This study provides a foundation for further research on the roles of BDH2 and iron metabolism in the pathogenesis of MDS.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1422-0067
1661-6596
Relation: https://www.mdpi.com/1422-0067/21/9/3033; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067
DOI: 10.3390/ijms21093033
URL الوصول: https://doaj.org/article/c7cebc9a93b44aa39db6cdd2518e7d7e
رقم الأكسشن: edsdoj.7cebc9a93b44aa39db6cdd2518e7d7e
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:14220067
16616596
DOI:10.3390/ijms21093033