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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

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • 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