ArticleNature medicine2018
Clonal heterogeneity of acute myeloid leukemia treated with the IDH2 inhibitor enasidenib.
Article in Nature medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01915498 (A Phase 1/2, Multicenter, Open-Label, Dose-Escalation and Expansion, Safety, Pharmacokinetic, Pharmacodynamic, and Clinical Activity Study of Orally Administered AG-221 in Subjects With Advanced Hematologic Malignancies With an IDH2 Mutation), which is not on this map. Cited by 119 papers.
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A Phase 1/2, Multicenter, Open-Label, Dose-Escalation and Expansion, Safety, Pharmacokinetic, Pharmacodynamic, and Clinical Activity Study of Orally Administered AG-221 in Subjects With Advanced Hematologic Malignancies With an IDH2 Mutation
Who cites it
119 citing papers in PubMed.
- Dynamic genetic and nongenetic RAS-pathway activation drives resistance to FLT3 and BCL2 inhibitor therapy.Blood · 2026Article
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- Predicting isocitrate dehydrogenase mutation status in acute myeloid leukemia from gene expression profiles by machine learning.NAR genomics and bioinformatics · 2026Article
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- Multiomic analysis of clonal development reveals new regulators of leukemic cell growth.Genes & development · 2026Article
- Resistance to Targeted Therapy in AML: Current Challenges and Emerging Treatment Strategies.Journal of clinical medicine · 2026Review
- MAPK Pathway Mutations Emerge in Mutant IDH1 Inhibitor-Resistant Cholangiocarcinoma and Attenuate the IFN Response.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Preserved IDH mutation and methylation class in vorasidenib nonresponders: A report of 2 cases.Neuro-oncology practice · 2026Article
- Identification of Bioactive Compounds and Molecular Targets of Compound Herbs Against Stomach Adenocarcinoma: A Network Pharmacology Approach.International journal of general medicine · 2026Article
- Enhancer heterogeneity in acute lymphoblastic leukemia drives differential gene expression in patients.Blood · 2025Article
- Genetic and Phenotypic Correlates of Clinical Outcomes with Venetoclax in Acute Myeloid Leukemia: The GEN-PHEN-VEN Study.Blood cancer discovery · 2025Article
- IMOP-Cancer: identifying mutation order pairs impacting cancer phenotypes.Briefings in bioinformatics · 2025Article
- Advances in IDH-mutant glioma management: IDH inhibitors, clinical implications of INDIGO trial, and future perspectives.Future oncology (London, England) · 2025Review
- The role of vorasidenib in the treatment of isocitrate dehydrogenase-mutant glioma.Neuro-oncology · 2025Review
- MutantProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Exome-wide association study reveals 7 functional variants associated with ex-vivo drug response in acute myeloid leukemia patients.BMC medical genomics · 2025Article
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- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- FLT3 targeting in the modern era: from clonal selection to combination therapies.International journal of hematology · 2024Review
59 more citing papers are in PubMed but not listed here.
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25 authors.
Funding
Abstract
Mutations in the gene encoding isocitrate dehydrogenase 2 (IDH2) occur in several types of cancer, including acute myeloid leukemia (AML). In model systems, mutant IDH2 causes hematopoietic differentiation arrest. Enasidenib, a selective small-molecule inhibitor of mutant IDH2, produces a clinical response in 40% of treated patients with relapsed/refractory AML by promoting leukemic cell differentiation. Here, we studied the clonal basis of response and acquired resistance to enasidenib treatment. Using sequential patient samples, we determined the clonal structure of hematopoietic cell populations at different stages of differentiation. Before therapy, IDH2-mutant clones showed variable differentiation arrest. Enasidenib treatment promoted hematopoietic differentiation from either terminal or ancestral mutant clones; less frequently, treatment promoted differentiation of nonmutant cells. Analysis of paired diagnosis/relapse samples did not identify second-site mutations in IDH2 at relapse. Instead, relapse arose by clonal evolution or selection of terminal or ancestral clones, thus highlighting multiple bypass pathways that could potentially be targeted to restore differentiation arrest. These results show how mapping of clonal structure in cell populations at different stages of differentiation can reveal the response and evolution of clones during treatment response and relapse.
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