Effect of IDH gene mutation on acute myeloid leukemia / 上海交通大学学报（医学版）

Isocitrate dehydrogenase (IDH) is an important metabolic enzyme involved in the tricarboxylic acid cycle. In recent years, IDH has become the most frequent tumor metabolic mutation gene in acute myeloid leukemia (AML). Unlike other mutations, it gains new functions which can catalyze α-ketoglutarate (α-KG) to produce the tumor metabolite D-2-hydroxyglutarate (D-2-HG). The increased D-2-HG in the cells can affect bone marrow cell differentiation and proliferation and induce myeloid tumors by the genetic controls, cell signaling, bone marrow microenvironment changes and other ways. Currently, the new IDH2 inhibitors AG-221 and IDH1 inhibitors become the first-line drugs targeted therapy in patients with IDH mutations in AML. This paper focused on the mutation of IDH and its mutation characteristics, the formation mechanism of AML by the metabolites produced by mutation, the metabolic pathway of tumor metabolites and the research progress of IDH inhibitors.

Application of Volumetric Analysis to Glioblastomas: a Correlation Study on the Status of the Isocitrate Dehydrogenase Mutation

PURPOSE: To investigate whether volumetric analysis based on T2WI and contrast-enhanced (CE) T1WI can distinguish between isocitrate dehydrogenase-1 mutation-positive (IDH1(P)) and -negative (IDH1(N)) glioblastomas (GBMs). MATERIALS AND METHODS: We retrospectively enrolled 109 patients with histopathologically proven GBMs after surgery or stereotactic biopsy and preoperative MR imaging. We measured the whole-tumor volume in each patient using a semiautomatic segmentation method based on both T2WI and CE T1WI. We compared the tumor volumes between IDH1(P) (n = 12) and IDH1(N) (n = 97) GBMs using an unpaired t-test. In addition, we performed receiver operating characteristic (ROC) analysis for the differentiation of IDH1(P) and IDH1(N) GBMs using the tumor volumes based on T2WI and CE T1WI. RESULTS: The mean tumor volume based on T2WI was larger for IDH1(P) GBMs than IDH1(N) GBMs (108.8 +/- 68.1 and 59.3 +/- 37.3 mm3, respectively, P = 0.0002). In addition, IDH1(P) GBMs had a larger tumor volume on CE T1WI than did IDH1(N) tumors (49.00 +/- 40.14 and 22.53 +/- 17.51 mm3, respectively, P < 0.0001). ROC analysis revealed that the tumor volume based on T2WI could distinguish IDH1(P) from IDH1(N) with a cutoff value of 90.25 (P < 0.05): 7 of 12 IDH1(P) (58.3%) and 79 of 97 IDH1(N) (81.4%). CONCLUSION: Volumetric analysis of T2WI and CE T1WI could enable IDH1(P) GBMs to be distinguished from IDH1(N) GBMs. We assumed that secondary GBMs with IDH1(P) underwent stepwise progression and were more infiltrative than those with IDH1(N), which might have resulted in the differences in tumor volume.

Isocitrate dehydrogenase gene mutations in intrahepatic cholangiocarcinoma / 中华肝胆外科杂志

Mutations in isocitrate dehydrogenase are among the most common genetic alterations in intrahepatic cholangiocarcinoma (ICC).Mutant IDH proteins in ICC and other malignancies acquire an abnormal enzymatic activity, allowing the conversion of alpha-ketoglutarate (alphaKG) to 2-hydroxyglutarate (2HG), which inhibits the activity of multiple alphaKG-dependent dioxygenases, and results in alterations in cell differentiation and tumorigenesis.This review will focus on recent advances, which may help understand the function of IDH mutation in intrahepatic cholangiocarcinoma.