Evidence map›Paper›PMID 10397723›Full record

ArticleBlood1999

C/EBPalpha bypasses granulocyte colony-stimulating factor signals to rapidly induce PU.1 gene expression, stimulate granulocytic differentiation, and limit proliferation in 32D cl3 myeloblasts.

X Wang, E Scott, C L Sawyers, A D Friedman

Abstract read
PubMed
In one paragraph

Article in Blood, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
4.4field-weighted citation impact, top 4% of its field
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

74 citing papers in PubMed, 165 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. The Ontogeny of a Neutrophil: Mechanisms of Granulopoiesis and Homeostasis.Microbiology and molecular biology reviews : MMBR · 2018
    Review
  6. Article
  7. 2014 Jeffrey M. Hoeg Award Lecture: Transcriptional Control of Monocyte Development.Arteriosclerosis, thrombosis, and vascular biology · 2016
    Review
  8. Article
  9. Article
  10. C/EBPα in normal and malignant myelopoiesis.International journal of hematology · 2015
    Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

X WangJohns Hopkins Oncology Center, Division of Pediatric Oncology, Baltimore, MD, USA.
E Scott
C L Sawyers
A D Friedman
Human Gene Therapy Research Institute · US

Funding

Analysis of PU.1 Function in HematopoiesisR01CA072769 · NCI · UNIVERSITY OF PENNSYLVANIA · PI SCOTT, EDWARD W · 1997 to 2007
$2.0M
NCI NIH HHS CA72769NHLBI NIH HHS HL15388
6 · The paper itself

Abstract

Within hematopoiesis, C/EBPalpha is expressed only in myeloid cells, and PU.1 is expressed mainly in myeloid and B-lymphoid cells. C/EBPalpha-deficient mice lack the neutrophil lineage and retain monocytes, whereas PU.1-deficient mice lack monocytes and have severely reduced neutrophils. We expressed a C/EBPalpha-estrogen receptor ligand-binding domain fusion protein, C/EBPalphaWT-ER, in 32D cl3 myeloblasts. 32D cl3 cells proliferate in interleukin-3 (IL-3) and differentiate to neutrophils in granulocyte colony-stimulating factor (G-CSF). In the presence of estradiol, C/EBPalphaWT-ER induced morphologic differentiation and the expression of the myeloperoxidase, lactoferrin, and G-CSF receptor mRNAs. C/EBPalphaWT-ER also induced a G1/S cell cycle block, with induction of p27 and Rb hypophosphorylation. bcr-ablp210 prevented 32D cl3 cell differentiation. Activation of C/EBPalpha-ER in 32D-bcr-ablp210 or Ba/F3 B-lymphoid cells induced cell cycle arrest independent of terminal differentiation. C/EBPalphaWT-ER induced endogenous PU.1 mRNA within 8 hours in both 32D cl3 and Ba/F3 cells, even in the presence of cycloheximide, indicating that C/EBPalpha directly activates the PU.1 gene. However, activation of a PU.1-ER fusion protein in 32D cl3 cells induced myeloperoxidase (MPO) RNA but not terminal differentiation. Thus, C/EBPalpha acts downstream of G-CSF and upstream of PU.1, p27, and potentially other factors to induce myeloblasts to undergo granulocytic differentiation and cell cycle arrest.

Indexed as

AnimalsCCAAT-Enhancer-Binding ProteinsCell CycleCell DifferentiationCell DivisionCells, CulturedDNA-Binding ProteinsGene Expression RegulationGranulocyte Colony-Stimulating FactorHematopoiesisHematopoietic Stem CellsInterleukin-3MiceNeutrophilsNuclear ProteinsProto-Oncogene ProteinsCCAAT-Enhancer-Binding ProteinsDNA-Binding ProteinsGranulocyte Colony-Stimulating FactorInterleukin-3Nuclear ProteinsProto-Oncogene ProteinsProto-Oncogene Protein Spi-1Recombinant Fusion ProteinsTrans-Activators

Identifiers

PMID10397723
OpenAlexW2132362370

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.