Rabbit Anti-Human IDH2 Polyclonal Antibody

Clonal hematopoiesis of indeterminate potential (CHIP) is linked to leukemia gene mutations and associates with an increased risk for coronary artery disease and poor prognosis in ischemic cardiomyopathy. Two recurrently mutated genes in CHIP and adult acute myeloid leukemia (AML) encode for isocitrate dehydrogenases 1 and 2 (IDH1andIDH2). Global expression of mutantIDH2in transgenic mice-induced dilated cardiomyopathy and muscular dystrophy. In this retrospective observational study, we investigated whether mutantIDH1/2predisposes to cardiovascular disease in AML patients. Among 363 AML patients,IDH1andIDH2mutations were detected in 26 (7.2%) and 39 patients (10.7%), respectively. MutantIDH1patients exhibited a significantly higher prevalence of coronary artery disease (26.1% vs. 6.4%,p = 0.002). Applying inverse probability-weighting analysis, patients withIDH1/2mutations had a higher risk for a declining cardiac function during AML treatment compared toIDH1/2wild type patients [left ventricular ejection fraction pretreatment compared to 10 months after diagnosis: 59.2% to 41.9% (p < 0.001) vs 58.5% to 55.4% (p = 0.27), respectively]. Mechanistically, RNA sequencing and immunostaining in hiPS-derived cardiomyocytes indicated that the oncometabolite R-2HG exacerbated doxorubicin mediated cardiotoxicity. Evaluation ofIDH1/2mutation status may therefore help identifying AML patients at risk for cardiovascular complications during cytotoxic treatment.

Introduction: The emergence of new omics approaches, such as genomic algorithms to identify tumor mutations and molecular modeling tools to predict the three-dimensional structure of proteins, has facilitated the understanding of the dynamic mechanisms involved in the pathogenesis of low-grade gliomas including oligodendrogliomas and astrocytomas. Methods: In this study, we targeted known mutations involved in low-grade gliomas, starting with the sequencing of genomic regions encompassing exon 4 of isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) and the four exons (5-6 and 7-8) of TP53 from 32 samples, followed by computational analysis to study the impact of these mutations on the structure and function of 3 proteins IDH1, IDH2, and p53. Results: We obtain a mutation that has an effect on the catalytic site of the protein IDH1 as R132H and on the catalytic site of the protein IDH2 as R172M. Other mutations at p53 have been identified as K305N, which is a pathogenic mutation; R175 H, which is a benign mutation; and R158G, which disrupts the structural conformation of the tumor suppressor protein. Conclusion: In low-grade gliomas, mutations in IDH1, IDH2, and TP53 may be the key to tumor progression because they have an effect on the function of the protein such as mutations R132H in IDH1 and R172M in IDH2, which change the function of the enzyme alpha-ketoglutarate, or R158G in TP53, which affects the structure of the generated protein, thus their importance in understanding gliomagenesis and for more accurate diagnosis complementary to the anatomical pathology tests.