IL10RA modulates crizotinib sensitivity in NPM1-ALK(+) anaplastic large cell lymphoma
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F20%3A00118318" target="_blank" >RIV/00216224:14740/20:00118318 - isvavai.cz</a>
Alternative codes found
RIV/65269705:_____/20:00073376
Result on the web
<a href="https://watermark.silverchair.com/bloodbld2019003793.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAA-owggPmBgkqhkiG9w0BBwagggPXMIID0wIBADCCA8wGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMMBbsGzlz9AIOl1NKAgEQgIIDnTVV8rPvZOJ1FU7OOHlmjO32rJ091T_ekg8" target="_blank" >https://watermark.silverchair.com/bloodbld2019003793.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAA-owggPmBgkqhkiG9w0BBwagggPXMIID0wIBADCCA8wGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMMBbsGzlz9AIOl1NKAgEQgIIDnTVV8rPvZOJ1FU7OOHlmjO32rJ091T_ekg8</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1182/blood.2019003793" target="_blank" >10.1182/blood.2019003793</a>
Alternative languages
Result language
angličtina
Original language name
IL10RA modulates crizotinib sensitivity in NPM1-ALK(+) anaplastic large cell lymphoma
Original language description
Anaplastic large cell lymphoma (ALCL) is a T-cell malignancy predominantly driven by a hyperactive anaplastic lymphoma kinase (ALK) fusion protein. ALK inhibitors, such as crizotinib, provide alternatives to standard chemotherapy with reduced toxicity and side effects. Children with lymphomas driven by nucleophosmin 1 (NPM1)-ALK fusion proteins achieved an objective response rate to ALK inhibition therapy of 54% to 90% in clinical trials; however, a subset of patients progressed within the first 3 months of treatment. The mechanism for the development of ALK inhibitor resistance is unknown. Through genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) activation and knockout screens in ALCL cell lines, combined with RNA sequencing data derived from ALK inhibitor-relapsed patient tumors, we show that resistance to ALK inhibition by crizotinib in ALCL can be driven by aberrant upregulation of interleukin 10 receptor subunit alpha (IL10RA). Elevated IL10RA expression rewires the STAT3 signaling pathway, bypassing otherwise critical phosphorylation by NPM1-ALK. IL-10RA expression does not correlate with response to standard chemotherapy in pediatric patients, suggesting that a combination of crizotinib and chemotherapy could prevent ALK inhibitor resistance-specific relapse.
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
30205 - Hematology
Result continuities
Project
<a href="/en/project/LQ1601" target="_blank" >LQ1601: CEITEC 2020</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
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
Blood
ISSN
0006-4971
e-ISSN
—
Volume of the periodical
136
Issue of the periodical within the volume
14
Country of publishing house
US - UNITED STATES
Number of pages
13
Pages from-to
1657-1669
UT code for WoS article
000579872400016
EID of the result in the Scopus database
2-s2.0-85090428303