Serum D-2-hydroxyglutarate and the ratio of D-2HG/L-2HG predict IDH mutation in acute myeloid leukemia

Chelsea Zhang; Andrew Chu; Richard Boriack; Robert Collins; Jing Xu; Dwight Oliver; Ruifang Zheng; Dinesh Rakheja; Weina Chen

doi:10.1002/jha2.723

Serum D-2-hydroxyglutarate and the ratio of D-2HG/L-2HG predict IDH mutation in acute myeloid leukemia

EJHaem. 2023 Jun 19;4(3):723-727. doi: 10.1002/jha2.723. eCollection 2023 Aug.

Authors

Chelsea Zhang¹, Andrew Chu¹, Richard Boriack², Robert Collins³, Jing Xu¹, Dwight Oliver¹, Ruifang Zheng¹, Dinesh Rakheja^{1

2}, Weina Chen¹

Affiliations

¹ Departments of Pathology University of Texas Southwestern Medical Center Dallas Texas USA.
² Children's Medical Center Dallas Dallas Texas USA.
³ Internal Medicine (Hematology and Oncology) University of Texas Southwestern Medical Center Dallas Texas USA.

Abstract

This study investigates whether serum D-2HG (D-2-hydroxyglutarate) produced by the mutated isocitrate dehydrogenase (IDH) can predict IDH mutations in acute myeloid leukemia (AML) at diagnosis. D-2HG and L-2HG are measured by liquid chromatography-tandem mass spectrometry. D-2HG, total 2HG and the D/L ratio (D-2HG/L-2HG) are significantly higher in IDH ^mutated cases than in IDH ^wild cases. The optimal cutoff values to predict IDH mutations at 100% sensitivity (specificity 91%-94%) are >588 ng/mL for D-2HG and >2.33 for the D/L ratio. Our study indicates that elevated serum D-2HG and the D/L ratio may serve as noninvasive biomarkers of IDH mutation in AML.

Keywords: D‐2HG/L‐2HG Ratio; D‐2‐Hydroxyglutarate; IDH; L‐2‐Hydroxyglutarate; acute myeloid leukemia.