Prospective serial evaluation of 2-hydroxyglutarate, during treatment of newly diagnosed acute myeloid leukemia, to assess disease activity and therapeutic response.

Amir T Fathi, Hossein Sadrzadeh, Darrell R Borger, Karen K Ballen, Philip C Amrein, Eyal C Attar, Julia Foster, Meghan Burke, Hector U Lopez, Christina R Matulis, Katherine M Edmonds, A John Iafrate, Kimberly S Straley, Katharine E Yen, Samuel Agresta, David P Schenkein, Cedric Hill, Ashkan Emadi, Donna S Neuberg, Richard M Stone, Yi-Bin Chen

Index: Blood 120(23) , 4649-52, (2012)

Full Text: HTML

Abstract

Mutations of genes encoding isocitrate dehydrogenase (IDH1 and IDH2) have been recently described in acute myeloid leukemia (AML). Serum and myeloblast samples from patients with IDH-mutant AML contain high levels of the metabolite 2-hydroxyglutarate (2-HG), a product of the altered IDH protein. In this prospective study, we sought to determine whether 2-HG can potentially serve as a noninvasive biomarker of disease burden through serial measurements in patients receiving conventional therapy for newly diagnosed AML. Our data demonstrate that serum, urine, marrow aspirate, and myeloblast 2-HG levels are significantly higher in IDH-mutant patients, with a correlation between baseline serum and urine 2-HG levels. Serum and urine 2-HG, along with IDH1/2-mutant allele burden in marrow, decreased with response to treatment. 2-HG decrease was more rapid with induction chemotherapy compared with DNA-methyltransferase inhibitor therapy. Our data suggest that serum or urine 2-HG may serve as noninvasive biomarkers of disease activity for IDH-mutant AML.