The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
IDH1(R132H) mutation increases murine haematopoietic progenitors and alters epigenetics
Open accessAbstract
Mutations in the IDH1 and IDH2 genes encoding isocitrate dehydrogenases are frequently found in human glioblastomas and cytogenetically normal acute myeloid leukaemias (AML). These alterations are gain-of-function mutations in that they drive the synthesis of the ‘oncometabolite’ R-2-hydroxyglutarate (2HG). It remains unclear how IDH1 and IDH2 mutations modify myeloid cell development and promote leukaemogenesis. Here we report the characterization of conditional knock-in (KI) mice in which the most common IDH1 mutation, IDH1(R132H), is inserted into the endogenous murine Idh1 locus and is expressed in all haematopoietic cells (Vav-KI mice) or specifically in cells of the myeloid lineage (LysM-KI mice). These mutants show increased numbers of early haematopoietic progenitors and develop splenomegaly and anaemia with extramedullary haematopoiesis, suggesting a dysfunctional bone marrow niche. Furthermore, LysM-KI cells have hypermethylated histones and changes to DNA methylation similar to those observed in human IDH1- or IDH2-mutant AML. To our knowledge, our study is the first to describe the generation and characterization of conditional IDH1(R132H)-KI mice, and also the first report to demonstrate the induction of a leukaemic DNA methylation signature in a mouse model. Our report thus sheds light on the mechanistic links between IDH1 mutation and human AML.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Furthermore, a knock-in of a mutant IDH1 allele into normal hematopoietic cells and into chondrocytes in vivo triggers an aberrant expansion of targeted cell lineages (Hirata et al., 2015; Sasaki et al., 2012).”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Sasaki et al., 2012
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482
Smyth, G. K. (2004) · Statistical Applications in Genetics and Molecular Biology · doi:10.2202/1544-6115.1027 · Cited by 11,829
The control of the false discovery rate in multiple testing under dependency
Benjamini, Y., & Yekutieli, D. (2001) · The Annals of Statistics · doi:10.1214/aos/1013699998 · Cited by 10,490
Statistical significance for genomewide studies
Storey, J. D., & Tibshirani, R. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1530509100 · Cited by 9,692
An Integrated Genomic Analysis of Human Glioblastoma Multiforme
Parsons, D. W., Jones, S., Zhang, X., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Siu, I.-M., Gallia, G. L., et al. (2008) · Science · doi:10.1126/science.1164382 · Cited by 5,857
Bismark: a flexible aligner and methylation caller for Bisulfite-Seq applications
Krueger, F., & Andrews, S. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr167 · Cited by 5,324
Cancer-associated IDH1 mutations produce 2-hydroxyglutarate
Dang, L., White, D. W., Gross, S., Bennett, B. D., Bittinger, M. A., Driggers, E. M., Fantin, V. R., Jang, H. G., Jin, S., Keenan, M. C., et al. (2009) · Nature · doi:10.1038/nature08617 · Cited by 4,154
Self-citationXu, W., Yang, H., Liu, Y., Yang, Y., Wang, P., Kim, S.-H., Ito, S., Yang, C., Wang, P., Xiao, M.-T., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2010.12.014 · Cited by 2,875
Figueroa, M. E., Abdel-Wahab, O., Lu, C., Ward, P. S., Patel, J., Shih, A., Li, Y., Bhagwat, N., Vasanthakumar, A., Fernandez, H. F., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.11.015 · Cited by 2,766
Self-citationIdentification of a CpG Island Methylator Phenotype that Defines a Distinct Subgroup of Glioma
Noushmehr, H., Weisenberger, D. J., Diefes, K., Phillips, H. S., Pujara, K., Berman, B. P., Pan, F., Pelloski, C. E., Sulman, E. P., Bhat, K. P., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.03.017 · Cited by 2,337
Cited by
Sorted by citations
The emerging hallmarks of cancer metabolism
Pavlova, N. N., & Thompson, C. B. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2015.12.006 · Cited by 5,926
Modulation of oxidative stress as an anticancer strategy
Gorrini, C., Harris, I. S., & Mak, T. W. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4002 · Cited by 3,579
Self-citationWallace, D. C. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3365 · Cited by 2,404
Understanding the Intersections between Metabolism and Cancer Biology
Heiden, M. G. V., & DeBerardinis, R. J. (2017) · Cell · doi:10.1016/j.cell.2016.12.039 · Cited by 2,369
Epigenetic Determinants of CancerPreprint
Baylin, S. B., & Jones, P. A. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a019505 · Cited by 1,414
Metadata
- Authors
- Sasaki, M., Knobbe, C. B., Munger, J. C., Lind, E. F., Brenner, D., Brüstle, A., Harris, I. S., Holmes, R., Wakeham, A., Haight, J., You-Ten, A., Li, W. Y., Schalm, S., Su, S. M., Virtanen, C., Reifenberger, G., Ohashi, P. S., Barber, D. L., Figueroa, M. E., Melnick, A., Zúñiga-Pflücker, J.-C., & Mak, T. W.
- Affiliations
- University Health Network (CA)
- University of Rochester Medicine (US)
- University of Toronto (CA)
- Agios Pharmaceuticals (United States) (US)
- Heinrich Heine University Düsseldorf (DE)
- Cornell University (US)
- Corresponding author
- Mak, Tak W.
- ORCID
- Venue
- Nature
- Published
- 2012-07-04
- Volume
- 488
- Issue
- 7413
- Pages
- 656-659
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4005896
- OpenAlex
- W2035409103
- Cited by
- 513
- References
- 34
- Citations by year
- 2026: 5 · 2025: 20 · 2024: 16 · 2023: 27 · 2022: 26 · 2021: 31 · 2020: 28 · 2019: 34 · 2018: 33 · 2017: 44 · 2016: 55 · 2015: 55 · 2014: 53 · 2013: 64 · 2012: 21
- FWCI
- 41.37
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- ANU Open Research (Australian National University) (submittedVersion)
- Funders
- Canadian Institutes of Health Research
- National Institute of Allergy and Infectious Diseases (R56AI081773, R01AI081773)
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- IDH1 R132H mutation, isocitrate dehydrogenase, 2-hydroxyglutarate, acute myeloid leukemia, hematopoietic progenitor cells, epigenetics, DNA methylation, histone methylation, conditional knock-in mice, extramedullary hematopoiesis, splenomegaly, anemia
- MeSH terms
- Aging, Animals, Bone Marrow, Disease Models, Animal, Female, Glioma, Hematopoiesis, Hematopoietic Stem Cells, Histones, Humans, Isocitrate Dehydrogenase, Male, Mutation, Spleen, Leukemia, Myeloid, Acute, CpG Islands, Cell Lineage, DNA Methylation, Myeloid Cells, Epigenesis, Genetic, Mutant Proteins, Mice, Gene Knock-In Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
