Evidence map›Paper›PMID 24089521›Full record

ArticleThe Journal of biological chemistry2013

The leukemia-associated Mll-Ell oncoprotein induces fibroblast growth factor 2 (Fgf2)-dependent cytokine hypersensitivity in myeloid progenitor cells.

Chirag A Shah, Ling Bei, Hao Wang, Leonidas C Platanias, Elizabeth A Eklund

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

12 citing papers in PubMed, 18 citations in OpenAlex.

  1. Review
  2. Article
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  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. HoxA10 Terminates Emergency Granulopoiesis by Increasing Expression of Triad1.Journal of immunology (Baltimore, Md. : 1950) · 2015
    Article
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  11. Article
  12. 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

5 authors at 2 institutions in 1 country.

Chirag A ShahFrom The Feinberg School of Medicine and Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois 60611.
Ling BeiFrom The Feinberg School of Medicine and Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois 60611; the Jesse Brown Veterans Administration Medical Center, Chicago, Illinois 60612.
Hao WangFrom The Feinberg School of Medicine and Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois 60611.
Leonidas C PlataniasFrom The Feinberg School of Medicine and Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois 60611; the Jesse Brown Veterans Administration Medical Center, Chicago, Illinois 60612.
Elizabeth A EklundFrom The Feinberg School of Medicine and Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois 60611; the Jesse Brown Veterans Administration Medical Center, Chicago, Illinois 60612. Electronic address: e-eklund@northwestern.edu.
Northwestern University · USJesse Brown VA Medical Center · US

Funding

Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LEONIDAS C. PLATANIAS · 1993 to 2026
$153.9M
Signal Transduction of Type I Interferons in Malignant CellsR01CA077816 · NCI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI PLATANIAS, LEONIDAS C. · 1998 to 2024
$6.6M
HoxA10 Function During Myeloid DifferentiationR01HL087717 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI EKLUND, ELIZABETH ANN · 2007 to 2011
$1.9M
The role of ICSBP in the pathogenesis of chronic myeloid leukemiaR01CA174205 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI EKLUND, ELIZABETH ANN · 2013 to 2017
$1.6M
Mnk Pathways and IFN-responses in Malignant CellsR01CA155566 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI PLATANIAS, LEONIDAS C. · 2011 to 2015
$1.6M
The role of emergency granulopoiesis in the pathogenesis of Fanconi AnemiaR01DK098812 · NIDDK · NORTHWESTERN UNIVERSITY AT CHICAGO · PI EKLUND, ELIZABETH ANN · 2014 to 2017
$1.3M
NCI NIH HHS CA155566NCI NIH HHS CA77816NCI NIH HHS P30 CA060553NCI NIH HHS R01 CA077816NCI NIH HHS R01 CA155566NCI NIH HHS R01 CA174205NHLBI NIH HHS HL87717NHLBI NIH HHS R01 HL087717NIDDK NIH HHS R01 DK098812
6 · The paper itself

Abstract

The subset of acute myeloid leukemias (AML) with chromosomal translocations involving the MLL gene have a poor prognosis (referred to as 11q23-AML). The MLL fusion proteins that are expressed in 11q23-AML facilitate transcription of a set of HOX genes, including HOXA9 and HOXA10. Because Hox proteins are transcription factors, this suggests the possibility that Hox target genes mediate the adverse effects of MLL fusion proteins in leukemia. Identifying such Hox target genes might provide insights to the pathogenesis and treatment of 11q23-AML. In the current study we found that Mll-Ell (an MLL fusion protein) induced transcriptional activation of the FGF2 gene in a HoxA9- and HoxA10-dependent manner. FGF2 encodes fibroblast growth factor 2 (also referred to as basic fibroblast growth factor). Fgf2 influences proliferation and survival of hematopoietic stem cells and myeloid progenitor cells, and increased Fgf2-expression has been described in AMLs. We determined that expression of Mll-Ell in myeloid progenitor cells resulted in autocrine production of Fgf2 and Fgf2-dependent cytokine hypersensitivity. Therefore, our results implicated increased Fgf2 expression in progenitor proliferation and expansion in 11q23-AML. Because small molecule inhibitors of Fgf-receptors are in human clinical trials, this suggested a potential therapeutic approach to this treatment refractory leukemia.

Indexed as

Autocrine CommunicationGene Expression Regulation, LeukemicTranscriptional ActivationAnimalsCytokinesFibroblast Growth Factor 2HumansLeukemia, Myeloid, AcuteMiceMice, KnockoutMyeloid-Lymphoid Leukemia ProteinMyeloid Progenitor CellsOncogene Proteins, FusionU937 CellsCytokinesFibroblast Growth Factor 2MLL-ELL fusion protein, humanMyeloid-Lymphoid Leukemia ProteinOncogene Proteins, FusionCell ProliferationFibroblast Growth Factor (FGF)Gene TranscriptionGrowth FactorshoxLeukemiamll

Identifiers

PMID24089521
PMCPMC3820883
OpenAlexW1982901636

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.