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. © 2013yang et al.; licensee biomed central ltd.