Human BDH2, an anti-apoptosis factor, is a novel poor prognostic factor for de novo cytogenetically normal acute myeloid leukemia.
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.
Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, No, 100 Tzyou 1st Road, 807 Kaohsiung, Taiwan. shlin@kmu.edu.tw.
Wen-Chi
WC
Yang
Wan-Chi
WC
Tsai
Pai-Mei
PM
Lin
Ming-Yu
MY
Yang
Yi-Chang
YC
Liu
Chao-Sung
CS
Chang
Wen-Hui
WH
Yu
Sheng-Fung
SF
Lin
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D002460:Cell Line; D002681:China / Q000453:epidemiology; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D055785:Gene Knockdown Techniques; D018922:HL-60 Cells; D006801:Humans; D006884:Hydroxybutyrate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D000090243:Nucleophosmin; D011379:Prognosis; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D055815:Young Adult
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; C000716967:NPM1 protein, human; D000077022:Survivin; D000090243:Nucleophosmin; C510607:BDH2 protein, human; D006884:Hydroxybutyrate Dehydrogenase