Evidence map›Paper›PMID 20215498›Full record

ArticleCancer research2010

Blockade of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase and murine double minute synergistically induces Apoptosis in acute myeloid leukemia via BH3-only proteins Puma and Bim.

Weiguo Zhang, Marina Konopleva, Jared K Burks, Karen C Dywer, Wendy D Schober, Jer-Yen Yang, Teresa J McQueen, Mien-Chie Hung, Michael Andreeff

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

Article in Cancer research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
3.3field-weighted citation impact, top 7% 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

47 citing papers in PubMed, 70 citations in OpenAlex.

  1. Review
  2. Article
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  4. Review
  5. Review
  6. Biomarkers of Response to Venetoclax Therapy in Acute Myeloid Leukemia.International journal of molecular sciences · 2024
    Review
  7. Small-molecule correctors and stabilizers to target p53.Trends in pharmacological sciences · 2023
    Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. Review
  15. Article
  16. Oncotarget · 2019
    Article
  17. Review
  18. Article
  19. Identification and Characterization of OncogenicMolecular cancer research : MCR · 2019
    Article
  20. 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

9 authors at 3 institutions in 2 countries.

Weiguo ZhangSection of Molecular Hematology and Therapy, Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030-4009, USA.
Marina Konopleva
Jared K Burks
Karen C Dywer
Wendy D Schober
Jer-Yen Yang
Teresa J McQueen
Mien-Chie Hung
Michael Andreeff
The University of Texas MD Anderson Cancer Center · USChina Medical University · TWChina Medical University Hospital · TW

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
University of Texas M.D. Anderson Cancer SPORE-LeukemiaP50CA100632 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI SHPALL, ELIZABETH J · 2003 to 2023
$43.7M
THE THERAPY OF AMLP01CA055164 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BERRY, DONALD A · 1992 to 2011
$25.3M
NCI NIH HHS CA016672NCI NIH HHS CA100632NCI NIH HHS CA55164NCI NIH HHS P01 CA055164NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA100632
6 · The paper itself

Abstract

Molecular aberrations of the Ras/Raf/mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK and/or Murine double minute (MDM2)/p53 signaling pathways have been reported in 80% and 50% of primary acute myeloid leukemia (AML) samples and confer poor outcome. In this study, antileukemic effects of combined MEK inhibition by AZD6244 and nongenotoxic p53 activation by MDM2 antagonist Nutlin-3a were investigated. Simultaneous blockade of MEK and MDM2 signaling by AZD6244 and Nutlin-3a triggered synergistic proapoptotic responses in AML cell lines [combination index (CI) = 0.06 +/- 0.03 and 0.43 +/- 0.03 in OCI/AML3 and MOLM13 cells, respectively] and in primary AML cells (CI = 0.52 +/- 0.01). Mechanistically, the combination upregulated levels of BH3-only proteins Puma and Bim, in part via transcriptional upregulation of the FOXO3a transcription factor. Suppression of Puma and Bim by short interfering RNA rescued OCI/AML3 cells from AZD/Nutlin-induced apoptosis. These results strongly indicate the therapeutic potential of combined MEK/MDM2 blockade in AML and implicate Puma and Bim as major regulators of AML cell survival.

Indexed as

Acute DiseaseApoptosisApoptosis Regulatory ProteinsBcl-2-Like Protein 11BenzimidazolesDrug SynergismExtracellular Signal-Regulated MAP KinasesForkhead Box Protein O3Forkhead Transcription FactorsHL-60 CellsHumansImidazolesLeukemia, MyeloidMAP Kinase Signaling SystemMembrane ProteinsMyeloid Cell Leukemia Sequence 1 ProteinApoptosis Regulatory ProteinsAZD 6244BBC3 protein, humanBCL2L11 protein, humanBcl-2-Like Protein 11BenzimidazolesExtracellular Signal-Regulated MAP KinasesForkhead Box Protein O3Forkhead Transcription FactorsFOXO3 protein, humanImidazolesMDM2 protein, humanMembrane ProteinsMyeloid Cell Leukemia Sequence 1 Proteinnutlin 3PiperazinesProto-Oncogene ProteinsProto-Oncogene Proteins c-bcl-2Proto-Oncogene Proteins c-mdm2

Identifiers

PMID20215498
PMCPMC2840060
OpenAlexW2096695840

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.