ArticleCell stem cell2025
Deconvoluting clonal and cellular architecture in IDH-mutant acute myeloid leukemia.
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Article in Cell stem cell, 2025. 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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17citing papers in PubMed
–field-weighted citation impact
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed.
- Type 1 interferon perturbates clonal competition by reshaping human blood development.Nature genetics · 2026Article
- A single-cell lens into the co-evolution of genotypes and phenotypes in cancer.Nature reviews. Cancer · 2026Review
- Therapy induced senescence promotes immunogenicity in acute myeloid Leukemia through reduced EZH2 activity.Nature communications · 2026Article
- Article
- Single-cell long-read genotyping of transcripts reveals discrete mechanisms of clonal evolution in post-MPN AML.Blood advances · 2026Article
- TCA-controlled histone succinylation identifies IDH3B as a prognostic and therapeutic target in AML.Clinical epigenetics · 2026Article
- Dynamics of IDH1/2 mutated clones in acute myeloid leukemia challenge their use as universal MRD markers.Blood cancer journal · 2026Article
- Accurate detection of tumor clonality and ongoing expansion mode from genomic data.bioRxiv : the preprint server for biology · 2026Article
- Article
- IDH1- and IDH2-mutated myeloid neoplasms: mutational pattern, clonal hierarchy, and the role in AML transformation.Blood advances · 2026Article
- Review
- APL-like subset withinHemaSphere · 2026Article
- Rare Gain-of-Function Variants in IDH1 and IDH2 Confer Increased Risk of Immune-Mediated Rheumatic Diseases.ACR open rheumatology · 2026Article
- 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
- Reframing-renaming(?)-myelodysplastic syndromes/neoplasms and clonal hematopoiesis of indeterminate potential.Leukemia · 2026Review
- Epigenetic reprogramming as the nexus of cancer stemness and therapy resistance: implications for biomarker discovery.Discover oncology · 2025Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
35 authors.
Maria SirenkoDepartment of Pathology, New York University Grossman School of Medicine, New York, NY, USA; Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY, USA; Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Computational Oncology Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Soobeom LeeDepartment of Pathology, New York University Grossman School of Medicine, New York, NY, USA; Department of Biology, New York University, New York, NY, USA.
Zhengxi SunDepartment of Pathology, New York University Grossman School of Medicine, New York, NY, USA; Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY, USA.
Ronan ChaligneProgram for Computational and Systems Biology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Sanam LoghaviDepartment of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Georgios AsimomitisComputational Oncology Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Biomedical Systems Laboratory, Department of Mechanical Engineering, National Technical University of Athens, Athens, Greece.
Charlotte K BrierleyMedical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK; NIHR Biomedical Research Centre, University of Oxford, Oxford, UK.
Elsa BernardComputational Oncology Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Sheng F CaiLeukemia Service, Department of Medicine, Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Robert M MyersTri-Institutional MD-PhD Program, Weill Cornell Medicine, Rockefeller University, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Bettina NadorpDepartment of Pathology, New York University Grossman School of Medicine, New York, NY, USA; Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY, USA; Division of Precision Medicine, Department of Medicine, New York University School of Medicine, New York, NY, USA.
Junya SangoDepartment of Oncological Sciences, Tisch Cancer Institute, Center for Advancement of Blood Cancer Therapies, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Morgan LalloVilcek Institute of Graduate Biomedical Sciences, NYU Grossman School of Medicine, New York, NY, USA.
Max F LevineComputational Oncology Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Dylan DomenicoComputational Oncology Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Juan E Arango OssaComputational Oncology Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Juan S Medina-MartinezComputational Oncology Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Kamal MenghrajaniLeukemia Service, Department of Medicine, Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Audrey LasryDepartment of Pathology, New York University Grossman School of Medicine, New York, NY, USA; Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY, USA.
Alice S MimsClara D. Bloomfield Center for Leukemia Outcomes Research, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA; Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
Helee DesaiClara D. Bloomfield Center for Leukemia Outcomes Research, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA; Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
Andrea LagansonClara D. Bloomfield Center for Leukemia Outcomes Research, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA; Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
Chris FamulareCenter for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Minal PatelCenter for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Gerard LozanskiDepartment of Pathology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
Kelly L BoltonDepartment of Medicine, Washington University, St. Louis, MO, USA.
Aaron D VinyColumbia Stem Cell Initiative, Columbia University Irving Medical Center, New York, NY, USA.
Mikhail RoshalHematopathology Diagnostic Service, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Ross L LevineLeukemia Service, Department of Medicine, Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Eirini P PapapetrouDepartment of Oncological Sciences, Tisch Cancer Institute, Center for Advancement of Blood Cancer Therapies, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Eytan M SteinLeukemia Service, Department of Medicine, Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Dan A LandauNew York Genome Center, New York, NY, USA; Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
Ann-Kathrin EisfeldClara D. Bloomfield Center for Leukemia Outcomes Research, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA; Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA; Pelotonia Institute for Immuno-Oncology, OSUCCC - James, The Ohio State University, Columbus, OH 43210, USA. Electronic address: ann-kathrin.eisfeld@osumc.edu.
Iannis AifantisDepartment of Pathology, New York University Grossman School of Medicine, New York, NY, USA; Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY, USA. Electronic address: ioannis.aifantis@nyulangone.org.
Elli PapaemmanuilComputational Oncology Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: papaemme@mskcc.org.
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4MTranslational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Daniel G. Stover · 1985 to 2026
$132.3MWeill Cornell/Rockefeller/Sloan-Kettering MST ProgramT32GM007739 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI HSU, KATHARINE C · 1985 to 2023
$51.1MThe impact of changes in chromatin architecture on cancer phenotypes and tumor progressionP01CA229086 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Giorgio Inghirami · 2019 to 2026
$17.0MThe Memorial Sloan Kettering Cancer Center SPORE in LeukemiaP50CA254838 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Eytan Stein · 2021 to 2026
$16.8MGenetic and molecular basis for SRSF2 mutations in myelodysplasiaR01HL128239 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Omar Abdel-Wahab, Robert K Bradley · 2015 to 2026
$8.0MXenotransplant and Genome Editing CoreU54DK126108 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI Daniel Starczynowski, YI ZHENG · 2021 to 2026
$5.0MMechanisms and therapeutic implications of human clonal hematopoiesis (CH) mutationsR01CA271331 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Eirini Papapetrou · 2022 to 2026
$3.3MImpact of mutational order on molecular mechanisms of oncogenesisR01CA260711 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Eirini Papapetrou · 2022 to 2026
$3.2MDissecting innate immune signaling in pre-leukemia evolutionR01CA271455 · NCI · CINCINNATI CHILDRENS HOSP MED CTR · PI Iannis Aifantis, Daniel Starczynowski · 2022 to 2026
$3.2MTargeting an RNA Binding Protein Network in Acute Myeloid LeukemiaR01CA242020 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI ABDEL-WAHAB, OMAR, AIFANTIS, IANNIS · 2020 to 2024
$2.7MCharting the differentiation topology of SF3B1 mutated clonal hematopoiesis (CH) and myelodysplastic syndromes (MDS) via a multi-omics single-cell toolkitR01HL157387 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI LANDAU, DAN · 2022 to 2025
$2.7MNCI NIH HHS F31 CA254130NCI NIH HHS K08 CA241371NCI NIH HHS P01 CA229086NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA016058NCI NIH HHS P50 CA254838NCI NIH HHS R01 CA228135NCI NIH HHS R01 CA242020NCI NIH HHS R01 CA260711NCI NIH HHS R01 CA262496NCI NIH HHS R01 CA266212NCI NIH HHS R01 CA271331NCI NIH HHS R01 CA271418NCI NIH HHS R01 CA271455NCI NIH HHS R01 CA283574NCI NIH HHS R01 CA284595NCI NIH HHS R01 CA298153NHLBI NIH HHS R01 HL128239NHLBI NIH HHS R01 HL157387NHLBI NIH HHS R01 HL159175NIDDK NIH HHS U54 DK126108NIGMS NIH HHS T32 GM007739NLM NIH HHS R01 LM013879
Abstract
Isocitrate dehydrogenase 1/2 (IDH) mutations are early initiating events in acute myeloid leukemia (AML). The complex clonal architecture and cellular heterogeneity in IDH-mutant AML underlies the heterogeneous clinical presentation and outcomes. Integrating single-cell genotyping and transcriptomics, we demonstrate a stem-like and inflammatory phenotype of IDH-mutant AML and identify clone-specific programs associated with NPM1, NRAS, and SRSF2 co-mutations. Furthermore, these clones had distinct responses to treatment with combination IDH inhibitors and chemotherapy, including elimination, reconstitution of myeloid differentiation, or retention within progenitor populations. At relapse after IDH inhibitor monotherapy, we identify upregulated stemness, inflammation, mitochondrial metabolism, and anti-apoptotic factors, as well as downregulated major histocompatibility complex (MHC) class II antigen presentation. At the pre-leukemic stage, we observe upregulation of IDH2-associated pathways, including inflammation. We deliver a detailed phenotyping of IDH-mutant AML and a framework for dissecting contributions of recurrently mutated genes in AML at diagnosis and following therapy, with implications for precision medicine.
Indexed as
Isocitrate DehydrogenaseLeukemia, Myeloid, AcuteMutationAnimalsClone CellsHumansNucleophosminIDH1 protein, humanIDH2 protein, humanIsocitrate DehydrogenaseNPM1 protein, humanNucleophosminacute myeloid leukemiacellular hierarchyclonal architectureclonal evolutionIDH1/2 mutationsIDH inhibitorsrelapsesingle-cell transcriptomicstargeted therapytreatment resistance
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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 Socratic graph.