The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Genomic and Epigenomic Landscapes of Adult De Novo Acute Myeloid Leukemia
Open accessAbstract
BACKGROUND: Many mutations that contribute to the pathogenesis of acute myeloid leukemia (AML) are undefined. The relationships between patterns of mutations and epigenetic phenotypes are not yet clear. METHODS: We analyzed the genomes of 200 clinically annotated adult cases of de novo AML, using either whole-genome sequencing (50 cases) or whole-exome sequencing (150 cases), along with RNA and microRNA sequencing and DNA-methylation analysis. RESULTS: AML genomes have fewer mutations than most other adult cancers, with an average of only 13 mutations found in genes. Of these, an average of 5 are in genes that are recurrently mutated in AML. A total of 23 genes were significantly mutated, and another 237 were mutated in two or more samples. Nearly all samples had at least 1 nonsynonymous mutation in one of nine categories of genes that are almost certainly relevant for pathogenesis, including transcription-factor fusions (18% of cases), the gene encoding nucleophosmin (NPM1) (27%), tumor-suppressor genes (16%), DNA-methylation-related genes (44%), signaling genes (59%), chromatin-modifying genes (30%), myeloid transcription-factor genes (22%), cohesin-complex genes (13%), and spliceosome-complex genes (14%). Patterns of cooperation and mutual exclusivity suggested strong biologic relationships among several of the genes and categories. CONCLUSIONS: We identified at least one potential driver mutation in nearly all AML samples and found that a complex interplay of genetic events contributes to AML pathogenesis in individual patients. The databases from this study are widely available to serve as a foundation for further investigations of AML pathogenesis, classification, and risk stratification. (Funded by the National Institutes of Health.).
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In the citing paper
“in line with clinical observations of adults and patients with myeloid malignancies typically lacking this oncogene (43).”
From PU.1-Dependent Enhancer Inhibition Separates Tet2 -Deficient Hematopoiesis from Malignant Transformation (2022) · cites this paper as [43]
Experimental — accuracy not yet measuredIn the citing paper
“both TET2 and TET3 are highly expressed in our model and in human AML27 (Supplementary Figure S2d).”
From Vitamin C-induced epigenomic remodelling in IDH1 mutant acute myeloid leukaemia (2018) · cites this paper as [27]
In the citing paper
“But many of the most commonly seen mutations in CHIP are also recurrent drivers of AML 64, myelodysplastic syndrome (MDS) 65–67, myeloproliferative neoplasms 68, and certain lymphomas 69,70.”
From Clonal hematopoiesis in human aging and disease (2019) · cites this paper as [64]
In the citing paper
“Treatment of AML with targeted therapies is particularly promising due to the fact that AMLs have far fewer mutations than most other adult cancers, with an average of only 13 mutations (Mardis et al, 2009; Cancer Genome Atlas Research Network, 2013).”
From Unlocking the potential of retinoic acid in anticancer therapy (2014) · cites this paper as Cancer Genome Atlas Research Network, 2013
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Circos: An information aesthetic for comparative genomicsPreprint
Krzywinski, M. I., Schein, J. E., Birol, İ., Connors, J. M., Gascoyne, R. D., Horsman, D. E., Jones, S. J. M., & Marra, M. A. (2009) · Genome Research · doi:10.1101/gr.092759.109 · Cited by 11,073
Döhner, H., Estey, E. H., Amadori, S., Appelbaum, F. R., Büchner, T., Burnett, A. K., Dombret, H., Fenaux, P., Grimwade, D. J., Larson, R. A., et al. (2009) · Blood · doi:10.1182/blood-2009-07-235358 · Cited by 3,438
MicroRNAs Modulate Hematopoietic Lineage Differentiation
Chen, C.-Z., Li, L., Lodish, H. F., & Bartel, D. P. (2004) · Science · doi:10.1126/science.1091903 · Cited by 3,257
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
Massive genomic rearrangement acquired in a single catastrophic event during cancer development
Stephens, P. J., Greenman, C. D., Fu, B., Yang, F., Bignell, G. R., Mudie, L. J., Pleasance, E. D., Lau, K. W., Beare, D., Stebbings, L. A., et al. (2011) · Cell · doi:10.1016/j.cell.2010.11.055 · Cited by 2,414
Recurring mutations found by sequencing an acute myeloid leukemia genome
Mardis, E. R., Ding, L., Dooling, D. J., Larson, D. E., McLellan, M. D., Chen, K., Koboldt, D. C., Fulton, R. S., Delehaunty, K. D., McGrath, S. D., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0903840 · Cited by 2,219
Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing
Ding, L., Ley, T. J., Larson, D. E., Miller, C. A., Koboldt, D. C., Welch, J. S., Ritchey, J. K., Young, M. A., Lamprecht, T., McLellan, M. D., et al. (2012) · Nature · doi:10.1038/nature10738 · Cited by 1,993
Prognostic Relevance of Integrated Genetic Profiling in Acute Myeloid Leukemia
Patel, J. P., Gönen, M., Figueroa, M. E., Fernandez, H. F., Sun, Z., Racevskis, J., Vlierberghe, P. V., Dolgalev, I., Thomas, S., Aminova, O., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1112304 · Cited by 1,990
DNMT3A Mutations in Acute Myeloid Leukemia
Ley, T. J., Ding, L., Walter, M. J., McLellan, M. D., Lamprecht, T., Larson, D. E., Kandoth, C., Payton, J. E., Baty, J., Welch, J., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1005143 · Cited by 1,983
Byrd, J. C. (2002) · Blood · doi:10.1182/blood-2002-03-0772 · Cited by 1,594
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Bone marrow inflammation in haematological malignancies
de Jong, M. M. E., Chen, L., Raaijmakers, M. H. G. P., & Cupedo, T. (2024) · Nature reviews. Immunology · doi:10.1038/s41577-024-01003-x · Cited by 54
Loss of Kat2a enhances transcriptional noise and depletes acute myeloid leukemia stem-like cells
Domingues, A. F., Kulkarni, R., Giotopoulos, G., Gupta, S., Vinnenberg, L., Arede, L., Foerner, E., Khalili, M., Adao, R. R., Johns, A., et al. (2020) · eLife · doi:10.7554/elife.51754 · Cited by 52
Sequencing-based measurable residual disease testing in acute myeloid leukemia
Yoest, J. M., Shirai, C. L., & Duncavage, E. J. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00249 · Cited by 48
“…between 15 and 30 coding region mutations including driver and passenger mutations; the large number of combinatorial mutation profiles makes inferring individualized risk at diagnosis based on published studies difficult (Cancer Genome Atlas Research Network et al., 2013; Cai and Levine, 2019).”
BackgroundInfluentialSmall-molecule correctors and stabilizers to target p53
Fallatah, M. M. J., Law, F. V., Chow, W. A., & Kaiser, P. (2023) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2023.02.007 · Cited by 44
Martinez-Høyer, S., Deng, Y., Parker, J., Jiang, J., Mo, A., Docking, T. R., Gharaee, N., Li, J., Umlandt, P., Fuller, M., et al. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0497-9 · Cited by 42
Nicosia, L., Boffo, F. L., Ceccacci, E., Conforti, F., Pallavicini, I., Bedin, F., Ravasio, R., Massignani, E., Somervaille, T. C. P., Minucci, S., et al. (2022) · Oncogene · doi:10.1038/s41388-021-02123-7 · Cited by 31
Gregoricchio, S., Polit, L., Esposito, M., Berthelet, J., Delestré, L., Evanno, E., Diop, M., Gallais, I., Aleth, H., Poplineau, M., et al. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac613 · Cited by 27
Aberrant GSK3β nuclear localization promotes AML growth and drug resistance
Ignatz-Hoover, J. J., Wang, V., Mackowski, N. M., Roe, A. J., Ghansah, I. K., Ueda, M., Lazarus, H. M., de Lima, M., Paietta, E., Fernandez, H., et al. (2018) · Blood Advances · doi:10.1182/bloodadvances.2018016006 · Cited by 27
Das, A. B., Smith-Díaz, C. C., & Vissers, M. C. M. (2020) · Haematologica · doi:10.3324/haematol.2020.259283 · Cited by 25
Garrett-Bakelman, F. E., & Melnick, A. M. (2016) · Epigenomics · doi:10.2217/epi-2016-0008 · Cited by 25
Aivalioti, M. M., Bartholdy, B. A., Pradhan, K., Bhagat, T. D., Zintiridou, A., Jeong, J. J., Thiruthuvanathan, V. J., Pujato, M., Paranjpe, A., Zhang, C., et al. (2022) · Blood Cancer Discovery · doi:10.1158/2643-3230.bcd-21-0226 · Cited by 22
“Yet, we did not find evidence for the presence of the ETV6–RUNX1 fusion gene in our compound mutant mice (Supplementary Table S8), in line with clinical observations of adults and patients with myeloid malignancies typically lacking this oncogene (43).”
ResultPTEN in Regulating Hematopoiesis and Leukemogenesis
Wu, Y., Zhu, H., & Wu, H. (2020) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a036244 · Cited by 22
Covalent Modifications of RUNX Proteins: Structure Affects Function
Blumenthal, E., Greenblatt, S., Huang, G., Ando, K., Xu, Y., & Nimer, S. D. (2017) · Advances in Experimental Medicine and Biology · doi:10.1007/978-981-10-3233-2_3 · Cited by 16
Biology and Therapeutic Properties of Mesenchymal Stem Cells in Leukemia
Wu, C.-H., Weng, T.-F., Li, J.-P., & Wu, K.-H. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25052527 · Cited by 13
Metadata
- Authors
- The Cancer Genome Atlas Research Network
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- The Cancer Genome Atlas Research Network
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2013-05-30
- Volume
- 368
- Issue
- 22
- Pages
- 2059-2074
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC3767041
- OpenAlex
- W1255676896
- Cited by
- 5,078
- References
- 49
- Citations by year
- 2026: 195 · 2025: 277 · 2024: 335 · 2023: 415 · 2022: 465 · 2021: 509 · 2020: 485 · 2019: 466 · 2018: 361 · 2017: 424 · 2016: 382 · 2015: 343 · 2014: 304 · 2013: 108
- FWCI
- 271.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- eSpace (Curtin University) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- National Institutes of Health
- National Human Genome Research Institute (U54HG003067, U54HG003079, U54HG003273, R01HG005690)
- National Cancer Institute (R01CA083962, U24CA143882, U24CA143843, U24CA143840, U24CA143858, U24CA144025, U24CA143866, U24CA143883, U24CA143845, R01CA162086, U24CA143867, U24CA143848, U24CA143799, U24CA143835, P01CA101937, P30CA016672, P30CA091842)
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- acute myeloid leukemia, de novo AML, adult AML, somatic mutations, epigenetics, DNA methylation, transcription factor fusion, NPM1, tumor suppressor, chromatin modifiers, driver mutations, risk stratification
- MeSH terms
- Nucleophosmin, Adult, Female, Humans, Male, Middle Aged, Mutation, Leukemia, Myeloid, Acute, Gene Expression, Genome, Human, Sequence Analysis, DNA, CpG Islands, DNA Methylation, MicroRNAs, Gene Fusion, Epigenomics
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