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@ARTICLE{Usenko:128462,
author = {T. Usenko and G. Chan and E. Torlakovic and U.
Klingmüller$^*$ and B. G. Neel},
title = {{L}eukemogenic {P}tpn11 allele causes defective
erythropoiesis in mice.},
journal = {PLoS one},
volume = {9},
number = {10},
issn = {1932-6203},
address = {Lawrence, Kan.},
publisher = {PLoS},
reportid = {DKFZ-2017-04478},
pages = {e109682 -},
year = {2014},
abstract = {Src homology 2 (SH2) domain-containing phosphatase 2
(SHP2), encoded by PTPN11, regulates signaling networks and
cell fate in many tissues. Expression of oncogenic PTPN11 in
the hematopoietic compartment causes myeloproliferative
neoplasm (MPN) in humans and mice. However, the
stage-specific effect(s) of mutant Ptpn11 on erythroid
development have remained unknown. We found that expression
of an activated, leukemogenic Ptpn11 allele, Ptpn11D61Y,
specifically in the erythroid lineage causes
dyserythropoiesis in mice. Ptpn11D61Y progenitors produce
excess cKIT+ CD71+ Ter119- cells and aberrant numbers of
cKITl° CD71+ erythroblasts. Mutant erythroblasts show
elevated activation of ERK, AKT and STAT3 in response to EPO
stimulation, and MEK inhibitor treatment blocks
Ptpn11D61Y-evoked erythroid hyperproliferation in vitro.
Thus, the expression of oncogenic Ptpn11 causes
dyserythropoiesis in a cell-autonomous manner in vivo.},
keywords = {Antigens, CD (NLM Chemicals) / Butadienes (NLM Chemicals) /
CD71 antigen (NLM Chemicals) / Nitriles (NLM Chemicals) /
Protein Kinase Inhibitors (NLM Chemicals) / Receptors,
Transferrin (NLM Chemicals) / STAT3 Transcription Factor
(NLM Chemicals) / Stat3 protein, mouse (NLM Chemicals) / U
0126 (NLM Chemicals) / Erythropoietin (NLM Chemicals) /
Proto-Oncogene Proteins c-kit (NLM Chemicals) /
Proto-Oncogene Proteins c-akt (NLM Chemicals) /
Extracellular Signal-Regulated MAP Kinases (NLM Chemicals) /
Protein Tyrosine Phosphatase, Non-Receptor Type 11 (NLM
Chemicals) / Ptpn11 protein, mouse (NLM Chemicals)},
cin = {A150},
ddc = {500},
cid = {I:(DE-He78)A150-20160331},
pnm = {311 - Signalling pathways, cell and tumor biology
(POF3-311)},
pid = {G:(DE-HGF)POF3-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:25289670},
pmc = {pmc:PMC4188809},
doi = {10.1371/journal.pone.0109682},
url = {https://inrepo02.dkfz.de/record/128462},
}