Evidence map›Paper›PMID 16847353›Full record

ArticleGenes & development2006

c-Myc is an important direct target of Notch1 in T-cell acute lymphoblastic leukemia/lymphoma.

Andrew P Weng, John M Millholland, Yumi Yashiro-Ohtani, Marie Laure Arcangeli, Arthur Lau, Carol Wai, Cristina Del Bianco, Carlos G Rodriguez, Hong Sai, John Tobias and 7 more

Erratum issuedOpen access · diamondAbstract read
In one paragraph

Article in Genes & development, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 479 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
479citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

479 citing papers in PubMed, 1 synthesis or guideline pooled it, 884 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. MYC: The Guardian of Its Own Chaos.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. T Cell Development: From T-Lineage Specification to Intrathymic Maturation.Advances in experimental medicine and biology · 2025
    Review
  12. Food for thought: Nutrient metabolism controlling early T cell development.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
  13. Drosophila as a Model for Metastasis.Advances in experimental medicine and biology · 2025
    Review
  14. Signaling pathway regulators in preimplantation embryos.Journal of molecular histology · 2024
    Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article

419 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

17 authors at 7 institutions in 2 countries.

Andrew P WengDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
John M Millholland
Yumi Yashiro-Ohtani
Marie Laure Arcangeli
Arthur Lau
Carol Wai
Cristina Del Bianco
Carlos G Rodriguez
Hong Sai
John Tobias
Yueming Li
Michael S Wolfe
Cathy Shachaf
Dean Felsher
Stephen C Blacklow
Warren S Pear
Jon C Aster
Cancer Research Institute · USHarvard University · USUniversity of Pennsylvania · USBrigham and Women's Hospital · USStanford University · USTerry Fox Research Institute · CAMemorial Sloan Kettering Cancer Center · US

Funding

IMMUNOBIOLOGY OF NORMAL AND NEOPLASTIC LYMPHOCYTEST32CA009140 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Malay Haldar, WARREN S PEAR · 1985 to 2026
$16.1M
Protein CoreP01CA119070 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ASTER, JON C. · 2006 to 2016
$10.3M
Structure and Function in Notch SignalingR01CA092433 · NCI · HARVARD MEDICAL SCHOOL · PI BLACKLOW, STEPHEN C. · 2002 to 2016
$5.0M
Structure and Function in Notch SignalingR56CA092433 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI BLACKLOW, STEPHEN C. · 2008 to 2008
$392k
Oncogenic Notch Signaling: Structural StudiesR01CA119130 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI BLACKLOW, STEPHEN C. · 2006 to 2006
$249k
NCI NIH HHS P01 CA119070NCI NIH HHS R01 CA092433NCI NIH HHS R01 CA119130NCI NIH HHS R56 CA092433NCI NIH HHS T32 CA009140NCI NIH HHS T32 CA 09140-31-35
6 · The paper itself

Abstract

Human acute T-cell lymphoblastic leukemias and lymphomas (T-ALL) are commonly associated with gain-of-function mutations in Notch1 that contribute to T-ALL induction and maintenance. Starting from an expression-profiling screen, we identified c-myc as a direct target of Notch1 in Notch-dependent T-ALL cell lines, in which Notch accounts for the majority of c-myc expression. In functional assays, inhibitors of c-myc interfere with the progrowth effects of activated Notch1, and enforced expression of c-myc rescues multiple Notch1-dependent T-ALL cell lines from Notch withdrawal. The existence of a Notch1-c-myc signaling axis was bolstered further by experiments using c-myc-dependent murine T-ALL cells, which are rescued from withdrawal of c-myc by retroviral transduction of activated Notch1. This Notch1-mediated rescue is associated with the up-regulation of endogenous murine c-myc and its downstream transcriptional targets, and the acquisition of sensitivity to Notch pathway inhibitors. Additionally, we show that primary murine thymocytes at the DN3 stage of development depend on ligand-induced Notch signaling to maintain c-myc expression. Together, these data implicate c-myc as a developmentally regulated direct downstream target of Notch1 that contributes to the growth of T-ALL cells.

Indexed as

Signal TransductionAnimalsCells, CulturedHumansLeukemia-Lymphoma, Adult T-CellMiceProto-Oncogene Proteins c-mycReceptor, Notch1Thymus GlandNOTCH1 protein, humanNotch1 protein, mouseProto-Oncogene Proteins c-mycReceptor, Notch1

Identifiers

PMID16847353
PMCPMC1536060
OpenAlexW2147373929

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.