Evidence map›Paper›PMID 25092144›Full record

ArticleLeukemia2015

NF-κB/STAT5/miR-155 network targets PU.1 in FLT3-ITD-driven acute myeloid leukemia.

D Gerloff, R Grundler, A A Wurm, D Bräuer-Hartmann, C Katzerke, J-U Hartmann, V Madan, C Müller-Tidow, J Duyster, D G Tenen and 2 more

Abstract read
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In one paragraph

Article in Leukemia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.

0numbers the graph read from it
0cells of the map it votes in
90citing papers in PubMed
3.8field-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

90 citing papers in PubMed, 134 citations in OpenAlex.

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

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

12 authors at 5 institutions in 2 countries.

D GerloffDivision of Hematology and Oncology, Leipzig University Hospital, Leipzig, Germany.
R GrundlerDepartment of Internal Medicine III, Technical University Munich, Munich, Germany.
A A WurmDivision of Hematology and Oncology, Leipzig University Hospital, Leipzig, Germany.
D Bräuer-HartmannDivision of Hematology and Oncology, Leipzig University Hospital, Leipzig, Germany.
C KatzerkeDivision of Hematology and Oncology, Leipzig University Hospital, Leipzig, Germany.
J-U HartmannDivision of Hematology and Oncology, Leipzig University Hospital, Leipzig, Germany.
V MadanCancer Science Institute, National University of Singapore, Singapore.
C Müller-TidowDepartment of Medicine IV, Hematology and Oncology, University of Halle, Halle, Germany.
J DuysterDepartment of Hematology/Oncology 1, University Medical Center Freiburg, Freiburg, Germany.
D G Tenen1] Cancer Science Institute, National University of Singapore, Singapore [2] Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA.
D NiederwieserDivision of Hematology and Oncology, Leipzig University Hospital, Leipzig, Germany.
G BehreDivision of Hematology and Oncology, Leipzig University Hospital, Leipzig, Germany.
University Hospital Leipzig · DELeipzig University · DENational University of Singapore · SGTechnical University of Munich · DEUniversity Medical Center Freiburg · DE

Funding

TYROSINE KINASE ONCOGENESIS IN MYELOID LEUKEMIAP01CA066996 · NCI · DANA-FARBER CANCER INSTITUTE · PI SCOTT A ARMSTRONG · 1996 to 2026
$52.5M
Molecular biology of myeloid differentiationR01HL112719 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI TENEN, DANIEL G · 2012 to 2015
$2.2M
Distinct acute myeloid leukemia subclasses with CEBPA mutationsR01CA118316 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI TENEN, DANIEL G · 2007 to 2011
$2.0M
NCI NIH HHS CA118316NCI NIH HHS P01 CA066996NCI NIH HHS R01 CA118316NHLBI NIH HHS R01 HL112719
6 · The paper itself

Abstract

Almost 30% of all acute myeloid leukemias (AML) are associated with an internal tandem duplication (ITD) in the juxtamembrane domain of FMS-like tyrosine kinase 3 receptor (FLT3). Patients with FLT3-ITD mutations tend to have a poor prognosis. MicroRNAs (miRNAs) have a pivotal role in myeloid differentiation and leukemia. MiRNA-155 (MiR-155) was found to be upregulated in FLT3-ITD-associated AMLs. In this study, we discovered that FLT3-ITD signaling induces the oncogenic miR-155. We show in vitro and in vivo that miR-155 expression is regulated by FLT3-ITD downstream targets nuclear factor-κB (p65) and signal transducer and activator of transcription 5 (STAT5). Further, we demonstrate that miR-155 targets the myeloid transcription factor PU.1. Knockdown of miR-155 or overexpression of PU.1 blocks proliferation and induces apoptosis of FLT3-ITD-associated leukemic cells. Our data demonstrate a novel network in which FLT3-ITD signaling induces oncogenic miR-155 by p65 and STAT5 in AML, thereby targeting transcription factor PU.1.

Indexed as

Gene Expression Regulation, LeukemicAdolescentAdultAgedAnimalsFemalefms-Like Tyrosine Kinase 3HumansLeukemia, Myeloid, AcuteMaleMiceMice, TransgenicMicroRNAsMiddle AgedMutationMyeloid CellsFLT3 protein, humanfms-Like Tyrosine Kinase 3MicroRNAsMIRN155 microRNA, humanProto-Oncogene ProteinsProto-Oncogene Protein Spi-1RNA, Small InterferingSTAT5 Transcription FactorTrans-ActivatorsTranscription Factor RelA

Identifiers

PMID25092144
PMCPMC4490787
OpenAlexW1972428122

What OpenQuestion holds

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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.