ArticleBlood2015
Genetic dissection of leukemia-associated IDH1 and IDH2 mutants and D-2-hydroxyglutarate in Drosophila.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- New alleles of D-2-hydroxyglutarate dehydrogenase enable studies of oncometabolite function in Drosophila melanogaster.G3 (Bethesda, Md.) · 2025Article
- The IDH1-R132H mutation aggravates cisplatin-induced acute kidney injury by promoting ferroptosis through disrupting NDUFA1 and FSP1 interaction.Cell death and differentiation · 2025Article
- Isocitrate Dehydrogenase Mutant Grade II and III Glial Neoplasms.Hematology/oncology clinics of North America · 2022Review
- IDH1 R132C and ERC2 L309I Mutations Contribute to the Development of Maffucci's Syndrome.Frontiers in endocrinology · 2021Article
- Physiological Signaling Functions of Reactive Oxygen Species in Stem Cells: From Flies to Man.Frontiers in cell and developmental biology · 2021Review
- The oncometabolite L-2-hydroxyglutarate is a common product of dipteran larval development.Insect biochemistry and molecular biology · 2020Article
- The significant role of redox system in myeloid leukemia: from pathogenesis to therapeutic applications.Biomarker research · 2020Review
- Glial Metabolic Rewiring Promotes Axon Regeneration and Functional Recovery in the Central Nervous System.Cell metabolism · 2020Article
- The Leukemic Fly: Promises and Challenges.Cells · 2020Review
- Review
- Drosophila melanogaster as a Model System for Human Glioblastomas.Advances in experimental medicine and biology · 2019Review
- Quantification of D- and L-2-Hydroxyglutarate in Drosophila melanogaster Tissue Samples Using Gas Chromatography-Mass Spectrometry.Methods in molecular biology (Clifton, N.J.) · 2019Article
- IDH1-mutated transgenic zebrafish lines: An in-vivo model for drug screening and functional analysis.PloS one · 2018Article
- Dissect new mechanistic insights for geniposide efficacy on the hepatoprotection using multiomics approach.Oncotarget · 2017Article
- Molecular Pathways: Isocitrate Dehydrogenase Mutations in Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Review
- D-2-hydroxyglutarate is essential for maintaining oncogenic property of mutant IDH-containing cancer cells but dispensable for cell growth.Oncotarget · 2015Article
- Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Gain-of-function mutations in nicotinamide adenine dinucleotide phosphate-dependent isocitrate dehydrogenase (IDH)1 and IDH2 frequently arise in human leukemias and other cancers and produce high levels of D-2-hydroxyglutarate (D-2HG). We expressed the R195H mutant of Drosophila Idh (CG7176), which is equivalent to the human cancer-associated IDH1-R132H mutant, in fly tissues using the UAS-Gal4 binary expression system. Idh-R195H caused a >25-fold elevation of D-2HG when expressed ubiquitously in flies. Expression of mutant Idh in larval blood cells (hemocytes) resulted in higher numbers of circulating blood cells. Mutant Idh expression in fly neurons resulted in neurologic and wing-expansion defects, and these phenotypes were rescued by genetic modulation of superoxide dismutase 2, p53, and apoptotic caspase cascade mediators. Idh-R163Q, which is homologous to the common leukemia-associated IDH2-R140Q mutant, resulted in moderately elevated D-2HG and milder phenotypes. We identified the fly homolog of D-2-hydroxyglutaric acid dehydrogenase (CG3835), which metabolizes D-2HG, and showed that coexpression of this enzyme with mutant Idh abolishes mutant Idh-associated phenotypes. These results provide a flexible model system to interrogate a cancer-related genetic and metabolic pathway and offer insights into the impact of IDH mutation and D-2HG on metazoan tissues.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.