AUTHOR=Han Fei , Zhao Huanhuan , Lu Jun , Yun Weina , Yang Lingling , Lou Yude , Su Dan , Chen Xin , Zhang Shixuan , Jin Hanwei , Li Xiang , Sun Jie , Huang He , Wang Qishan , Jiang Xi 

TITLE=Anti-Tumor Effects of BDH1 in Acute Myeloid Leukemia

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.694594

DOI=10.3389/fonc.2021.694594

ISSN=2234-943X

ABSTRACT=<p>Dysregulation of ketone metabolism has been reported in various types of cancer. In order to find out its role in acute myeloid leukemia (AML) pathogenesis, we first analyzed the expression levels of 10 key genes involved in ketone metabolism in AML blasts and CD34<sup>+</sup> hematopoietic stem cells (HSCs) from healthy donors. We found that the expression level of <italic>BDH1</italic> was significantly lower in AML than in normal HSCs. The downregulation of <italic>BDH1</italic> gene expression in AML cell lines as compared with normal HSCs was further confirmed with real-time RT-PCR. Analysis of TCGA and other database revealed that the downregulation of <italic>BDH1</italic> was associated with worse prognosis in AML patients. In addition, we showed that overexpression of <italic>BDH1</italic> inhibited the viability and proliferation of AML cells. In contrast, <italic>BDH1</italic> knock-down promoted AML cell growth. Collectively, our results suggest the previously unappreciated anti-tumor role of <italic>BDH1</italic> in AML, and low <italic>BDH1</italic> expression predicts poor survival.</p>