LymphedemaV1, Ncbi, Checkpoint, bibRecord, 008714

GATA Factor-Dependent Positive-Feedback Circuit in Acute Myeloid Leukemia Cells

Identifieur interne : 008714 ( Ncbi/Checkpoint ); précédent : 008713; suivant : 008715

GATA Factor-Dependent Positive-Feedback Circuit in Acute Myeloid Leukemia Cells

Auteurs : Koichi R. Katsumura [États-Unis] ; Irene M. Ong [États-Unis] ; Andrew W. Devilbiss [États-Unis] ; Rajendran Sanalkumar [États-Unis] ; Emery H. Bresnick [États-Unis]

Source :

Cell reports [ 2211-1247 ] ; 2016.

RBID : PMC:5154384

Abstract

SUMMARY

The master regulatory transcription factor GATA-2 triggers hematopoietic stem and progenitor cell generation. GATA2 haploinsufficiency is implicated in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), and GATA2 overexpression portends a poor prognosis for AML. However, the constituents of the GATA-2-dependent genetic network mediating pathogenesis are unknown. We described a p38-dependent mechanism that phosphorylates GATA-2 and increases GATA-2 target gene activation. We demonstrate that this mechanism establishes a growth-promoting chemokine/cytokine circuit in AML cells. p38/ERK-dependent GATA-2 phosphorylation facilitated positive autoregulation of GATA2 transcription and expression of target genes, including IL1B and CXCL2. IL-1β and CXCL2 enhanced GATA-2 phosphorylation, which increased GATA-2-mediated transcriptional activation. p38/ERK-GATA-2 stimulated AML cell proliferation via CXCL2 induction. As GATA2 mRNA correlated with IL1B and CXCL2 mRNAs in AML-M5 and high expression of these genes predicted poor prognosis of cyto-genetically normal AML, we propose that the circuit is functionally important in specific AML contexts.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5154384

DOI: 10.1016/j.celrep.2016.07.058
PubMed: 27545880
PubMed Central: 5154384

Affiliations:

États-Unis

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PMC:5154384

Le document en format XML

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<front><div type="abstract" xml:lang="en"><title>SUMMARY</title>
<p id="P2">The master regulatory transcription factor GATA-2 triggers hematopoietic stem and progenitor cell generation. <italic>GATA2</italic>
 haploinsufficiency is implicated in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), and GATA2 overexpression portends a poor prognosis for AML. However, the constituents of the GATA-2-dependent genetic network mediating pathogenesis are unknown. We described a p38-dependent mechanism that phosphorylates GATA-2 and increases GATA-2 target gene activation. We demonstrate that this mechanism establishes a growth-promoting chemokine/cytokine circuit in AML cells. p38/ERK-dependent GATA-2 phosphorylation facilitated positive autoregulation of <italic>GATA2</italic>
 transcription and expression of target genes, including <italic>IL1B</italic>
 and <italic>CXCL2</italic>
. IL-1β and CXCL2 enhanced GATA-2 phosphorylation, which increased GATA-2-mediated transcriptional activation. p38/ERK-GATA-2 stimulated AML cell proliferation via CXCL2 induction. As <italic>GATA2</italic>
 mRNA correlated with <italic>IL1B</italic>
 and <italic>CXCL2</italic>
 mRNAs in AML-M5 and high expression of these genes predicted poor prognosis of cyto-genetically normal AML, we propose that the circuit is functionally important in specific AML contexts.</p>
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<name sortKey="Bresnick, Emery H" sort="Bresnick, Emery H" uniqKey="Bresnick E" first="Emery H." last="Bresnick">Emery H. Bresnick</name>
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<name sortKey="Devilbiss, Andrew W" sort="Devilbiss, Andrew W" uniqKey="Devilbiss A" first="Andrew W." last="Devilbiss">Andrew W. Devilbiss</name>
<name sortKey="Devilbiss, Andrew W" sort="Devilbiss, Andrew W" uniqKey="Devilbiss A" first="Andrew W." last="Devilbiss">Andrew W. Devilbiss</name>
<name sortKey="Katsumura, Koichi R" sort="Katsumura, Koichi R" uniqKey="Katsumura K" first="Koichi R." last="Katsumura">Koichi R. Katsumura</name>
<name sortKey="Ong, Irene M" sort="Ong, Irene M" uniqKey="Ong I" first="Irene M." last="Ong">Irene M. Ong</name>
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<name sortKey="Sanalkumar, Rajendran" sort="Sanalkumar, Rajendran" uniqKey="Sanalkumar R" first="Rajendran" last="Sanalkumar">Rajendran Sanalkumar</name>
<name sortKey="Sanalkumar, Rajendran" sort="Sanalkumar, Rajendran" uniqKey="Sanalkumar R" first="Rajendran" last="Sanalkumar">Rajendran Sanalkumar</name>
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GATA Factor-Dependent Positive-Feedback Circuit in Acute Myeloid Leukemia Cells

GATA Factor-Dependent Positive-Feedback Circuit in Acute Myeloid Leukemia Cells

Source :

Abstract

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Links to Exploration step

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