Cited by 405Genomics and Chromatin DynamicsAcute Lymphoblastic Leukemia researchDevelopmental Biology and Gene Regulation

A NOTCH1-driven MYC enhancer promotes T cell development, transformation and acute lymphoblastic leukemia

Open access
Herranz, Daniel, Ambesi-Impiombato, Alberto, Palomero, Teresa, Schnell, Stephanie A, Belver, Laura, Wendorff, Agnieszka A, Xu, Luyao, Castillo-Martin, Mireia +5 more·2014·Nature Medicine

Abstract

Efforts to identify and annotate cancer driver genetic lesions have been focused primarily on the analysis of protein-coding genes; however, most genetic abnormalities found in human cancer are located in intergenic regions. Here we identify a new long range-acting MYC enhancer controlled by NOTCH1 that is targeted by recurrent chromosomal duplications in human T cell acute lymphoblastic leukemia (T-ALL). This highly conserved regulatory element, hereby named N-Me for NOTCH MYC enhancer, is located within a broad super-enhancer region +1.47 Mb from the MYC transcription initiating site, interacts with the MYC proximal promoter and induces orientation-independent MYC expression in reporter assays. Moreover, analysis of N-Me knockout mice demonstrates a selective and essential role of this regulatory element during thymocyte development and in NOTCH1-induced T-ALL. Together these results identify N-Me as a long-range oncogenic enhancer implicated directly in the pathogenesis of human leukemia and highlight the importance of the NOTCH1-MYC regulatory axis in T cell transformation and as a therapeutic target in T-ALL.

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/nm.3665

Cites

60 of 60 references verified0 citation errors · 0 not checkable

Statistics

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.

A few free checks a day · papers already verified open instantly · results are public

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Herranz, D., Ambesi-Impiombato, A., Palomero, T., Schnell, S. A., Belver, L., Wendorff, A. A., Xu, L., Castillo-Martin, M., Llobet-Navás, D., Cordon-Cardo, C., Clappier, E., Soulier, J., & Ferrando, A. A.
Affiliations
  • Columbia University (US)
  • Columbia University Irving Medical Center (US)
  • Inserm (FR)
Corresponding author
Ferrando, Adolfo A
Venue
Nature Medicine
Published
2014-09-07
Volume
20
Issue
10
Pages
1130-1137
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
OpenAlex
W2091517552
Cited by
405
References
60
Citations by year
2026: 14 · 2025: 21 · 2024: 29 · 2023: 30 · 2022: 43 · 2021: 48 · 2020: 38 · 2019: 40 · 2018: 45 · 2017: 39 · 2016: 29 · 2015: 24 · 2014: 3
FWCI
12.99
Type
journal article
Language
en
Open access
Locations
  • Nature Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Agence Nationale de la Recherche (ANR-10-IBHU-0002)
  • National Cancer Institute (P01CA087497, R01CA120196, CA120196)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Acute Lymphoblastic Leukemia research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
Notch1, T-cell acute lymphoblastic leukemia, T cell development, chromosomal duplication, super-enhancers, long-range enhancers, T-cell transformation, therapeutic target
MeSH terms
Animals, Cell Transformation, Neoplastic, Enhancer Elements, Genetic, Female, Gene Amplification, Humans, Male, Mice, Inbred C57BL, Oncogenes, T-Lymphocytes, Neoplastic Stem Cells, Genes, myc, Mice, Knockout, Jurkat Cells, Lymphopoiesis, Cell Line, Tumor, Mice, Receptor, Notch1, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

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