Abstract
BackgroundThe 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.ResultsWe 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.ConclusionsBDH2 is a novel independent poor prognostic marker for CN-AML, with the role of anti-apoptosis, through surviving.
Highlights
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 Nucleophosmin 1 (NPM1), FLT3, and CCAAT/enhancer binding protein (CEBPA) as a complement to cytogenetic information within both the World Health Organization and the European Leukemia Net classifications
While Type 2-hydroxybutyrate dehydrogenase (BDH2) is a gene related to mitochondria metabolism and participates in LCN2 mediated iron transport and apoptosis, we have interest to know if BDH2 has prognostic impact on cytogenetically normal AML (CN-AML)
Association of BDH2 expression with molecular markers and clinical characteristics The mRNA expression of BDH2 was higher in patients with CN-AML and poor risk than in those with normal bone marrow (BM) (P < 0.001, Figure 1 and Additional file 1: Figure S1)
Summary
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. 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. BDH2 catalyzes the production of 2, 3-DHBA during enterobactin biosynthesis and participates in 24p3 (LCN2)-mediated iron transport and apoptosis. Clonal chromosomal aberrations are not detected in 40–50% of patients [1] Both the World Health Organization and the European Leukemia Net classifications have included molecular markers such. Devireddy et al reported that BDH2 catalyzes the production of 2,3-DHBA during enterobactin biosynthesis and participates in 24p3 (LCN2)-mediated iron transport and apoptosis [22]. While BDH2 is a gene related to mitochondria metabolism and participates in LCN2 mediated iron transport and apoptosis, we have interest to know if BDH2 has prognostic impact on CN-AML
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