- 作者: Wen-Chi Yang, Wan-Chi Tsai, Pai-Mei Lin, Ming-Yu Yang, Yi-Chang Liu, Chao-Sung Chang, Wen-Hui Yu and Sheng-Fung Lin
- 作者服務機構: Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100 Tzyou 1st Road, 807 Kaohsiung, Taiwan, R.O.C
- 中文摘要: --
- 英文摘要:
Background: The relevance of recurrent molecular abnormalities in cytogenetically normal (CN) acute myeloid leukemia (AML) was recently acknowledged by the inclusion of molecular markers such as NPM1, FLT3, and CEBPA as a complement to cytogenetic information within both the World Health Organization and the European Leukemia Net classifications. Mitochondrial metabolism is different in cancer and normal cells. A novel cytosolic type 2-hydroxybutyrate dehydrogenase, BDH2, originally named DHRS6, plays a physiological role in the cytosolic utilization of ketone bodies, which can subsequently enter mitochondria and the tricarboxylic acid cycle. Moreover, BDH2 catalyzes the production of 2, 3-DHBA during enterobactin biosynthesis and participates in 24p3 (LCN2)-mediated iron transport and apoptosis.
Results: We observed that BDH2 expression is an independent poor prognostic factor for CN-AML, with an anti-apoptotic role. Patients with high BDH2 expression have relatively shorter overall survival (P = 0.007) and a low complete response rate (P = 0.032). BDH2-knockdown (BDH2-KD) in THP1 and HL60 cells increased the apoptosis rate under reactive oxygen species stimulation. Decrease inducible survivin, a member of the inhibitors of apoptosis family, but not members of the Bcl-2 family, induced apoptosis via a caspase-3-independent pathway upon BDH2-KD.
Conclusions: BDH2 is a novel independent poor prognostic marker for CN-AML, with the role of anti-apoptosis, through surviving. - 中文關鍵字: --
- 英文關鍵字: BDH2, Survivin, Cytogenetically normal acute myeloid leukemia, Prognosis, Survival, Apoptosis