Evidence map›Paper›PMID 27211267›Full record

ArticleLeukemia2016

Small molecule inhibition of cAMP response element binding protein in human acute myeloid leukemia cells.

B Mitton, H-D Chae, K Hsu, R Dutta, G Aldana-Masangkay, R Ferrari, K Davis, B C Tiu, A Kaul, N Lacayo and 10 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Leukemia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
4.1field-weighted citation impact, top 6% 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

32 citing papers in PubMed, 43 citations in OpenAlex.

  1. Article
  2. Review
  3. cAMP response element-binding protein: A credible cancer drug target.The Journal of pharmacology and experimental therapeutics · 2025
    Review
  4. Fluorine-Thiol Displacement Stapling on the Disordered αSynlett : accounts and rapid communications in synthetic organic chemistry · 2025
    Article
  5. Article
  6. Review
  7. Cyclic AMP-regulatory element-binding protein: a novel UV-targeted transcription factor in skin cancer.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2024
    Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Complex roles of cAMP-PKA-CREB signaling in cancer.Experimental hematology & oncology · 2020
    Review
  17. What turns CREB on? And off? And why does it matter?Cellular and molecular life sciences : CMLS · 2020
    Review
  18. Article
  19. Article
  20. Targeting transcription factors in acute myeloid leukemia.International journal of hematology · 2019
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors at 4 institutions in 1 country.

B MittonDepartment of Pediatrics, Stanford University, Stanford, CA, USA.
H-D ChaeDepartment of Pediatrics, Stanford University, Stanford, CA, USA.
K HsuDepartment of Pediatrics, Stanford University, Stanford, CA, USA.
R DuttaDepartment of Pediatrics, Stanford University, Stanford, CA, USA.
G Aldana-MasangkayDepartment of Pediatrics, Stanford University, Stanford, CA, USA.
R FerrariDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.
K DavisDepartment of Pediatrics, Stanford University, Stanford, CA, USA.
B C TiuDepartment of Pediatrics, Stanford University, Stanford, CA, USA.
A KaulDepartment of Pediatrics, Stanford University, Stanford, CA, USA.
N LacayoDepartment of Pediatrics, Stanford University, Stanford, CA, USA.
G DahlDepartment of Pediatrics, Stanford University, Stanford, CA, USA.
F XieDepartment of Physiology and Pharmacology, Oregon Health and Sciences University, Portland, OR, USA.
B X LiDepartment of Physiology and Pharmacology, Oregon Health and Sciences University, Portland, OR, USA.
M R BreeseDepartment of Pediatrics, Stanford University, Stanford, CA, USA.
E M LandawDepartment of Biomathematics, University of California, Los Angeles, Los Angeles, CA, USA.
G NolanDepartment of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
M PellegriniDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.ORCID 0000-0001-9355-9564
S RomanovNanosyn, Inc., Santa Clara, CA, USA.
X XiaoDepartment of Physiology and Pharmacology, Oregon Health and Sciences University, Portland, OR, USA.
K M SakamotoDepartment of Pediatrics, Stanford University, Stanford, CA, USA.
Stanford University · USOregon Health & Science University · USUniversity of California, Los Angeles · USNanosyn (United States) · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
Systems Biology CoreU19AI100627 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI ULEVITCH, RICHARD J · 2012 to 2021
$49.1M
The Role of CREB in Normal Myelopoiesis and LeukemogenesisR01HL075826 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SAKAMOTO, KATHLEEN M · 2004 to 2013
$3.2M
Chemical Inhibitors of CREB-mediated Gene TranscriptionR01GM087305 · NIGMS · OREGON HEALTH & SCIENCE UNIVERSITY · PI XIAO, XIANGSHU · 2010 to 2014
$1.6M
NCI NIH HHS P30 CA016042NHLBI NIH HHS R01 HL075826NIAID NIH HHS U19 AI100627NIGMS NIH HHS R01 GM087305
6 · The paper itself

Abstract

The transcription factor CREB (cAMP Response-Element Binding Protein) is overexpressed in the majority of acute myeloid leukemia (AML) patients, and this is associated with a worse prognosis. Previous work revealed that CREB overexpression augmented AML cell growth, while CREB knockdown disrupted key AML cell functions in vitro. In contrast, CREB knockdown had no effect on long-term hematopoietic stem cell activity in mouse transduction/transplantation assays. Together, these studies position CREB as a promising drug target for AML. To test this concept, a small molecule inhibitor of CREB, XX-650-23, was developed. This molecule blocks a critical interaction between CREB and its required co-activator CBP (CREB Binding Protein), leading to disruption of CREB-driven gene expression. Inhibition of CBP-CREB interaction induced apoptosis and cell-cycle arrest in AML cells, and prolonged survival in vivo in mice injected with human AML cells. XX-650-23 had little toxicity on normal human hematopoietic cells and tissues in mice. To understand the mechanism of XX-650-23, we performed RNA-seq, ChIP-seq and Cytometry Time of Flight with human AML cells. Our results demonstrate that small molecule inhibition of CBP-CREB interaction mostly affects apoptotic, cell-cycle and survival pathways, which may represent a novel approach for AML therapy.

Indexed as

AnimalsAntineoplastic AgentsApoptosisCell Cycle CheckpointsCell Line, TumorCREB-Binding ProteinHeterograftsHumansLeukemia, Myeloid, AcuteMicePeptide FragmentsProtein BindingSialoglycoproteinsSurvival RateAntineoplastic Agentsbone sialoprotein (35-62), humanCREB-Binding ProteinCREBBP protein, humanPeptide FragmentsSialoglycoproteins

Identifiers

PMID27211267
PMCPMC5143163
OpenAlexW2396128094

What OpenQuestion holds

Textmetadata
LicenceTDM
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.