OBJECTIVE: To investigate the predictive value of morphology, immunology, and cytogenetics for isocitrate dehydrogenase 1 and 2 (IDH1/2) gene mutation in newly diagnosed acute myeloid leukemia (AML) patients. METHODS: The clinical data of 186 newly diagnosed AML patients (except M3 subtype) in the First People's Hospital of Changzhou were retrospectively analyzed, and the variables associated with IDH1/2 mutation in patients were screened using LASSO regression to construct a multivariate logistic regression analysis model. The Bootstrap method was used for internal validation of the model and nomograms were used to visualize the model, and receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of the model. RESULTS: A total of 60 AML patients had IDH1/2 mutation at initial diagnosis. LASSO regression screened 9 predictive variables associated with IDH1/2 mutation, including CD7, CD56, CD11b, CD15, CD64, HLA-DR, platelet count≥50×10⁹/L, isolated +8 and normal karyotype. The nomogram and ROC curve were plotted based on the above 9 variables. The area under the ROC curve (AUC) of the training set and the validation set were 0.871 and 0.806, respectively. Internal validation showed that the nomogram had good predictive ability. CONCLUSION The prediction model based on MIC typing constructed in this study has a good predictive ability for the presence of IDH1/2 mutations in newly diagnosed AML patients and has important clinical application value when the gene mutation detection results are unavailable.
Humans ; Isocitrate Dehydrogenase/genetics* ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Retrospective Studies ; Nomograms ; Female ; Male ; ROC Curve ; Middle Aged

Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. Isocitrate dehydrogenase (IDH) is a key enzyme in the tricarboxylic acid cycle and one of the common mutated genes in AML. Although the 2022 version of the ELN guidelines suggests that IDH mutations cannot be used as a separate prognostic stratification indicator, multiple studies have indicated that IDH mutations have prognostic significance for AML. Early identification of IDH mutations and selection of appropriate treatment options are crucial. This review summarizes the research progress on the characteristics, carcinogenic mechanisms, prognosis of IDH mutations in AML patients, and treatment options, in order to provide reference for further improving the prognosis of IDH -mutated AML patients.
Humans ; Isocitrate Dehydrogenase/genetics* ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Prognosis

Metabolic reprogramming, a newly recognized trait of tumor biology, is an intensively studied prospect for oncology medicines. For numerous tumors and cancer cell subpopulations, oxidative phosphorylation (OXPHOS) is essential for their biosynthetic and bioenergetic functions. Cancer cells with mutations in isocitrate dehydrogenase 1 (IDH1) exhibit differentiation arrest, epigenetic and transcriptional reprogramming, and sensitivity to mitochondrial OXPHOS inhibitors. In this study, we report that berberine, which is widely used in China to treat intestinal infections, acted solely at the mitochondrial electron transport chain (ETC) complex I, and that its association with IDH1 mutant inhibitor (IDH1^mi) AG-120 decreased mitochondrial activity and enhanced antileukemic effect in vitro andin vivo. Our study gives a scientific rationale for the therapy of IDH1 mutant acute myeloid leukemia (AML) patients using combinatory mitochondrial targeted medicines, particularly those who are resistant to or relapsing from IDH1^mi.
Humans ; Oxidative Phosphorylation ; Berberine ; Electron Transport ; Mitochondria ; Leukemia, Myeloid, Acute ; Isocitrate Dehydrogenase

Yeast autolysis affects the flavor and quality of beer. The regulation of yeast autolysis is a need for industrial beer production. Previous studies on brewer's yeast autolysis showed that the citric acid cycle-related genes had a great influence on yeast autolysis. To explore the contribution of isocitrate dehydrogenase genes in autolysis, the IDP1 and IDP2 genes were destroyed or overexpressed in typical lager yeast Pilsner. The destruction of IDP1 gene improved the anti-autolytic ability of yeast, and the anti-autolytic index after 96 h autolysis was 8.40, 1.5 times higher than that of the original strain. The destruction of IDP1 gene increased the supply of nicotinamide adenine dinucleotide phosphate (NADPH) and the NADPH/NADP⁺ ratio was 1.94. After fermentation, intracellular ATP level was 1.8 times higher than that of the original strain, while reactive oxygen species (ROS) was reduced by 10%. The destruction of IDP2 gene resulted in rapid autolysis and a decrease in the supply of NADPH. Anti-autolytic index after 96 h autolysis was 4.03 and the NADPH/NADP⁺ ratio was 0.89. After fermentation, intracellular ATP level was reduced by 8% compared with original strain, ROS was 1.3 times higher than that of the original strain. The results may help understand the regulation mechanism of citric acid cycle-related genes on yeast autolysis and provide a basis for the selection of excellent yeast with controllable anti-autolytic performance.
Humans ; Isocitrate Dehydrogenase/genetics* ; NADP ; Reactive Oxygen Species ; Autolysis ; Adenosine Triphosphate

Antineoplastic Combined Chemotherapy Protocols ; Azacitidine/therapeutic use* ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Humans ; Isocitrate Dehydrogenase/therapeutic use* ; Leukemia, Myeloid, Acute/genetics* ; Nuclear Proteins ; Sulfonamides

Isocitrate dehydrogenase (IDH) is an essential metabolic enzyme in the tricarboxylic acid cycle (TAC). The high mutation frequency of the IDH gene plays a complicated role in gliomas. In addition to affecting gliomas directly, mutations in IDH can also alter their immune microenvironment and can change immune-cell function in direct and indirect ways. IDH mutations mediate immune-cell infiltration and function by modulating immune-checkpoint gene expression and chemokine secretion. In addition, IDH mutation-derived D2-hydroxyglutarate can be absorbed by surrounding immune cells, also affecting their functioning. In this review, we summarize current knowledge about the effects of IDH mutations as well as other gene mutations on the immune microenvironment of gliomas. We also describe recent preclinical and clinical data related to IDH-mutant inhibitors for the treatment of gliomas. Finally, we discuss different types of immunotherapy and the immunotherapeutic potential of IDH mutations in gliomas.
Brain Neoplasms/therapy* ; Glioma/therapy* ; Humans ; Immunotherapy ; Isocitrate Dehydrogenase/genetics* ; Mutation/genetics* ; Tumor Microenvironment

OBJECTIVE: To explore the coexisting mutations in IDH-mutated acute myeloid leukemia(AML) and its relation with partial clinical parametrs. METHODS: The exon 4 mutation of IDH1/2 gene was screened by using genome DNA-PCR combined with sanger sequencing, 51 targeted gene mutations in the patients with IDH1/2 mutation were detected by using high throughput DNA sequencing combined with sanger sequencing. RESULTS: Among 358 patients, the IDH1/2 mutation was found in 46 cases including IDH1 mutation in 35 cases and IDH2 mutation in 11 cases, 97.87%(45/46) patients with IDH1/2 mutation simultaneously carried other gene mutations including 8(17.8%) cases with mutation of double gene, 17(37.8%) cases with mutation of 3 genes and 20(44.4%) cases with mutation of ≥ 4 genes. The mutation frequency of each patient averaged 3.52 times. In mutation of accompanied genes, the common genes were NPM1(n=29, 63.0%), next DNMT3A(n=25, 54.3%), FLT3-ITD(n=7, 15.2%), TET2(n=5, 10.9%) and NRAS(n=5, 10.9%). The average WBC level of patients with NPM1 mutation in IDH1 mutation group was higher than that of patients in wild type group(P<0.05). The complete remission (CR) rate of patients with DNMT3A mutation was significant lower than that of patients with wild type (30% vs 80%, P<0.01). The presence of ≥ 4 mutations was found to be significantly associated with higher white blood level than that in the patients with double mutations(P<0.05). CONCLUSION More than 95% AML patients with IDH1/2 mutation commonly show additional mutations. The number and the type of IDH coexisting mutations have certain effect on the clinical features and CR rate.
Exons ; Humans ; Isocitrate Dehydrogenase ; genetics ; Leukemia, Myeloid, Acute ; genetics ; Mutation ; Prognosis ; Remission Induction

Abstract　　 Demethylating agents (HMAs) hold an important status in therapy for elderly acute myeloid leukemia, who are not eligible for intensive chemotherapy (ICT). Beyond the edge of monotherapy, domestic and foreign scholars have carried out a lot of studies on combination strategies, such as HMAs with low-intensity therapy (G-CSF, low-dose cytarabine and aclarubicin, CAG), with targeted therapy (BCL-2 inhibitor), with immunotherapy (immune checkpoint inhibitors, ICI), and with other epigenetic therapys (isocitrate dehydrogenase or histonedeacetylase inhibitor）. Some of these researches have obtained positive results and discussed the mechanisms of combination strategies besides. In this review, the combination of HMAs with other drugs are summraized briefly.
Aclarubicin ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; Cytarabine ; Granulocyte Colony-Stimulating Factor ; Humans ; Isocitrate Dehydrogenase ; Leukemia, Myeloid, Acute

To investigate the clinical value of serum tumor marker isocitrate dehydrogenase 1(IDH1)in the diagnosis of lung cancer. The general data were collected in lung cancer patients and non-lung cancer patients.The serum level of IDH1 was detected by enzyme-linked immunosorbent assay to evaluate its clinical significance in diagnosing lung cancer. The serum IDH1 level was significantly higher in lung cancer patients than in non-lung cancer patients [(7.12±6.98)ng/ml (2.09±1.83)ng/ml,=11.540,<0.001].The serum IDH1 level in patients with adenocarcinoma or squamous cell carcinoma was significantly higher than that in patients with small cell lung cancer [(7.91±7.26)ng/ml (2.76±2.27)ng/ml, =6.345,<0.001].The sensitivity of IDH1 in detecting lung cancer,stage Ⅰ/Ⅱ lung cancer,and stage Ⅲ/Ⅳ lung cancer was 47.4%,49.1%,and 46.3%,respectively. Serum IDH1 has high sensitivities and specificities in the diagnosis and differential diagnosis of non-small cell lung cancer(squamous cell carcinoma and adenocarcinoma)and small cell lung cancer as well as the auxiliary diagnosis of stage Ⅰ and Ⅱ lung cancer.It is a valuable marker for the auxiliary diagnosis of lung cancer.
Biomarkers, Tumor ; Carcinoma, Non-Small-Cell Lung ; Humans ; Isocitrate Dehydrogenase ; blood ; Lung Neoplasms

Glutamate leads to neuronal cell damage by generating neurotoxicity during brain development. The objective of this study is to identify proteins that differently expressed by glutamate treatment in neonatal cerebral cortex. Sprague-Dawley rat pups (post-natal day 7) were intraperitoneally injected with vehicle or glutamate (10 mg/kg). Brain tissues were isolated 4 h after drug treatment and fixed for morphological study. Moreover, cerebral cortices were collected for protein study. Two-dimensional gel electrophoresis and mass spectrometry were carried out to identify specific proteins. We observed severe histopathological changes in glutamate-exposed cerebral cortex. We identified various proteins that differentially expressed by glutamate exposure. Identified proteins were thioredoxin, peroxiredoxin 5, ubiquitin carboxy-terminal hydrolase L1, proteasome subunit alpha proteins, isocitrate dehydrogenase, and heat shock protein 60. Heat shock protein 60 was increased in glutamate exposed condition. However, other proteins were decreased in glutamate-treated animals. These proteins are related to anti-oxidant, protein degradation, metabolism, signal transduction, and anti-apoptotic function. Thus, our findings can suggest that glutamate leads to neonatal cerebral cortex damage by regulation of specific proteins that mediated with various functions.
Animals ; Brain ; Cerebral Cortex ; Chaperonin 60 ; Electrophoresis, Gel, Two-Dimensional ; Glutamic Acid ; Humans ; Infant, Newborn ; Isocitrate Dehydrogenase ; Mass Spectrometry ; Metabolism ; Neurons ; Peroxiredoxins ; Proteasome Endopeptidase Complex ; Proteolysis ; Proteomics ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Thioredoxins ; Ubiquitin Thiolesterase