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

被引：99

作者：

Fathi, Amir T. ^{[1
]}

Sadrzadeh, Hossein ^{[1
]}

Borger, Darrell R. ^{[1
]}

Ballen, Karen K. ^{[1
]}

Amrein, Philip C. ^{[1
]}

Attar, Eyal C. ^{[1
]}

Foster, Julia ^{[1
]}

Burke, Meghan ^{[1
]}

Lopez, Hector U. ^{[1
]}

Matulis, Christina R. ^{[1
]}

Edmonds, Katherine M. ^{[1
]}

Iafrate, A. John ^{[1
]}

Straley, Kimberly S. ^{[2
]}

Yen, Katharine E. ^{[2
]}

Agresta, Samuel ^{[2
]}

Schenkein, David P. ^{[2
]}

Hill, Cedric ^{[1
]}

Emadi, Ashkan ^{[3
]}

Neuberg, Donna S. ^{[4
]}

Stone, Richard M. ^{[4
]}

Chen, Yi-Bin ^{[1
]}

机构：

[1] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA

[2] Agios Pharmaceut, Cambridge, MA USA

[3] Univ Maryland, Med Ctr, Greenebaum Canc Ctr, Baltimore, MD 21201 USA

[4] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02114 USA

来源：

BLOOD | 2012年 / 120卷 / 23期

关键词：

ISOCITRATE DEHYDROGENASE 1; IDH2; MUTATIONS; CONVERSION;

D O I：

10.1182/blood-2012-06-438267

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 mar-row, 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. (Blood. 2012; 120(23):4649-4652)

引用

页码：4649 / 4652

页数：4

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