Erythropoiesis defect observed in STAT3 GOF patients with severe anemia
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F20%3A10410767" target="_blank" >RIV/00216208:11130/20:10410767 - isvavai.cz</a>
Alternative codes found
RIV/00064203:_____/20:10410767
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=jMfv_tjjk5" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=jMfv_tjjk5</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.jaci.2019.11.042" target="_blank" >10.1016/j.jaci.2019.11.042</a>
Alternative languages
Result language
angličtina
Original language name
Erythropoiesis defect observed in STAT3 GOF patients with severe anemia
Original language description
In summary, we reveal that STAT3 activity in patients carrying the P715L-STAT3 mutation can be modulated by either IL-6 stimulation or targeted inhibition. Furthermore, based on our findings in cell lines, P715L-STAT3 is not constitutively active in patients carrying the mutation. In these patients, STAT3 interacts with proinflammatory binding partners. Finally, P715L-STAT3 GOF manifests with faster kinetic and prolonged STAT3 phosphorylation, causing deviated STAT5 activity in our in vitro model of hematopoiesis. This imbalance in STATs' activity suppresses erythropoietic capacity as evidenced by low erythropoietic potential of peripheral CD342 precursors. The chronic state of severe anemia seen in P1 was accompanied by oligoclonal lymphoid infiltrates in the BM. This observation, together with successful treatment of pure red cell aplasia using a combination of high-dose methylprednisolone, IL-6R inhibitor, and cyclosporine A after the use of a JAK inhibitor, shows that this chronic state of severe anemia can be reversed. This indicates that erythropoiesis in patients with STAT3 GOF mutations is a system under strain, in which inflammatory triggers may unbalance erythroid differentiation and suppress proliferative capacity of red blood cell precursors, rendering patients less able to respond with stress erythropoiesis.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30102 - Immunology
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Allergy and Clinical Immunology
ISSN
0091-6749
e-ISSN
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Volume of the periodical
145
Issue of the periodical within the volume
4
Country of publishing house
US - UNITED STATES
Number of pages
5
Pages from-to
1297-1301
UT code for WoS article
000523633400028
EID of the result in the Scopus database
2-s2.0-85078157735