Human BDH2, an anti-apoptosis factor, is a novel poor prognostic factor for de novo cytogenetically normal acute myeloid leukemia

J Biomed Sci. 2013 Aug 14;20(1):58. doi: 10.1186/1423-0127-20-58.


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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis
  • Cell Line
  • China / epidemiology
  • Female
  • Gene Expression Regulation, Leukemic*
  • Gene Knockdown Techniques
  • HL-60 Cells
  • Humans
  • Hydroxybutyrate Dehydrogenase / genetics*
  • Hydroxybutyrate Dehydrogenase / metabolism
  • Inhibitor of Apoptosis Proteins / metabolism
  • Leukemia, Myeloid, Acute / diagnosis*
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / mortality
  • Male
  • Middle Aged
  • Nucleophosmin
  • Prognosis
  • RNA Interference
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survivin
  • Young Adult


  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • NPM1 protein, human
  • Survivin
  • Nucleophosmin
  • BDH2 protein, human
  • Hydroxybutyrate Dehydrogenase