IL10RA modulates crizotinib sensitivity in NPM1-ALK(+)
anaplastic large cell lymphoma

J 2020

IL10RA modulates crizotinib sensitivity in NPM1-ALK(+) anaplastic large cell lymphoma

PROKOPH, N., N.A. PROBST, L.C. LEE, J.M. MONAHAN, J.D. MATTHEWS et. al.

Basic information

Original name

IL10RA modulates crizotinib sensitivity in NPM1-ALK(+) anaplastic large cell lymphoma

Authors

PROKOPH, N., N.A. PROBST, L.C. LEE, J.M. MONAHAN, J.D. MATTHEWS, H.C. LIANG, K. BAHNSEN, I.A. MONTES-MOJARRO, E. KARACA-ATABAY, G.G. SHARMA, V. MALIK, H. LAROSE, S.D. FORDE, S.P. DUCRAY, Cosimo LOBELLO (380 Italy, belonging to the institution), Q. WANG, S.L. LUAN, Šárka POSPÍŠILOVÁ (203 Czech Republic, guarantor, belonging to the institution), C. GAMBACORTI-PASSERINI, G.A.A. BURKE, S. PERVEZ, A. ATTARBASCHI, A. JANIKOVA, H. PACQUEMENT, J. LANDMAN-PARKER, A. LAMBILLIOTTE, G. SCHLEIERMACHER, W. KLAPPER, R. JAUCH, W. WOESSMANN, G. VASSAL, L. KENNER, O. MERKEL, L. MOLOGNI, R. CHIARLE, L. BRUGIERES, B. GEOERGER, I. BARBIERI and Suzanne Dawn TURNER (826 United Kingdom of Great Britain and Northern Ireland, belonging to the institution)

Edition

Blood, Washington DC, USA, American Society of Hematology, 2020, 0006-4971

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 22.113

RIV identification code

RIV/00216224:14740/20:00118318

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1182/blood.2019003793

UT WoS

000579872400016

Keywords in English

NON-HODGKIN-LYMPHOMA; MOLECULAR SIGNATURES; PEDIATRIC-PATIENTS; TYROSINE KINASE; SOLID TUMORS; ALK; EXPRESSION; CHILDREN; ADOLESCENTS; GENE

Abstract

V originále

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.

Links

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

675712, interní kód MU

Name: ALK Activation as a target of TRAanslational Science (ALKATRAS): Break free from cancer (Acronym: ALKATRAS)

Investor: European Union, MSCA Marie Skłodowska-Curie Actions (Excellent Science)

Citovat

PROKOPH, N., N.A. PROBST, L.C. LEE, J.M. MONAHAN, J.D. MATTHEWS, H.C. LIANG, K. BAHNSEN, I.A. MONTES-MOJARRO, E. KARACA-ATABAY, G.G. SHARMA, V. MALIK, H. LAROSE, S.D. FORDE, S.P. DUCRAY, Cosimo LOBELLO, Q. WANG, S.L. LUAN, Šárka POSPÍŠILOVÁ, C. GAMBACORTI-PASSERINI, G.A.A. BURKE, S. PERVEZ, A. ATTARBASCHI, A. JANIKOVA, H. PACQUEMENT, J. LANDMAN-PARKER, A. LAMBILLIOTTE, G. SCHLEIERMACHER, W. KLAPPER, R. JAUCH, W. WOESSMANN, G. VASSAL, L. KENNER, O. MERKEL, L. MOLOGNI, R. CHIARLE, L. BRUGIERES, B. GEOERGER, I. BARBIERI and Suzanne Dawn TURNER. IL10RA modulates crizotinib sensitivity in NPM1-ALK(+) anaplastic large cell lymphoma. Blood. Washington DC, USA: American Society of Hematology, 2020, vol. 136, No 14, p. 1657-1669. ISSN 0006-4971. Available from: https://dx.doi.org/10.1182/blood.2019003793.

@article{1748838,
   author = {Prokoph, N. and Probst, N.A. and Lee, L.C. and Monahan, J.M. and Matthews, J.D. and Liang, H.C. and Bahnsen, K. and MontesandMojarro, I.A. and KaracaandAtabay, E. and Sharma, G.G. and Malik, V. and Larose, H. and Forde, S.D. and Ducray, S.P. and Lobello, Cosimo and Wang, Q. and Luan, S.L. and Pospíšilová, Šárka and GambacortiandPasserini, C. and Burke, G.A.A. and Pervez, S. and Attarbaschi, A. and Janikova, A. and Pacquement, H. and LandmanandParker, J. and Lambilliotte, A. and Schleiermacher, G. and Klapper, W. and Jauch, R. and Woessmann, W. and Vassal, G. and Kenner, L. and Merkel, O. and Mologni, L. and Chiarle, R. and Brugieres, L. and Geoerger, B. and Barbieri, I. and Turner, Suzanne Dawn},
   article_location = {Washington DC, USA},
   article_number = {14},
   doi = {http://dx.doi.org/10.1182/blood.2019003793},
   keywords = {NON-HODGKIN-LYMPHOMA; MOLECULAR SIGNATURES; PEDIATRIC-PATIENTS; TYROSINE KINASE; SOLID TUMORS; ALK; EXPRESSION; CHILDREN; ADOLESCENTS; GENE},
   language = {eng},
   issn = {0006-4971},
   journal = {Blood},
   title = {IL10RA modulates crizotinib sensitivity in NPM1-ALK(+) anaplastic large cell lymphoma},
   url = {https://watermark.silverchair.com/bloodbld2019003793.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAA-owggPmBgkqhkiG9w0BBwagggPXMIID0wIBADCCA8wGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMMBbsGzlz9AIOl1NKAgEQgIIDnTVV8rPvZOJ1FU7OOHlmjO32rJ091T_ekg8},
   volume = {136},
   year = {2020}
}

TY  - JOUR
ID  - 1748838
AU  - Prokoph, N. - Probst, N.A. - Lee, L.C. - Monahan, J.M. - Matthews, J.D. - Liang, H.C. - Bahnsen, K. - Montes-Mojarro, I.A. - Karaca-Atabay, E. - Sharma, G.G. - Malik, V. - Larose, H. - Forde, S.D. - Ducray, S.P. - Lobello, Cosimo - Wang, Q. - Luan, S.L. - Pospíšilová, Šárka - Gambacorti-Passerini, C. - Burke, G.A.A. - Pervez, S. - Attarbaschi, A. - Janikova, A. - Pacquement, H. - Landman-Parker, J. - Lambilliotte, A. - Schleiermacher, G. - Klapper, W. - Jauch, R. - Woessmann, W. - Vassal, G. - Kenner, L. - Merkel, O. - Mologni, L. - Chiarle, R. - Brugieres, L. - Geoerger, B. - Barbieri, I. - Turner, Suzanne Dawn
PY  - 2020
TI  - IL10RA modulates crizotinib sensitivity in NPM1-ALK(+) anaplastic large cell lymphoma
JF  - Blood
VL  - 136
IS  - 14
SP  - 1657-1669
EP  - 1657-1669
PB  - American Society of Hematology
SN  - 00064971
KW  - NON-HODGKIN-LYMPHOMA
KW  - MOLECULAR SIGNATURES
KW  - PEDIATRIC-PATIENTS
KW  - TYROSINE KINASE
KW  - SOLID TUMORS
KW  - ALK
KW  - EXPRESSION
KW  - CHILDREN
KW  - ADOLESCENTS
KW  - GENE
UR  - https://watermark.silverchair.com/bloodbld2019003793.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAA-owggPmBgkqhkiG9w0BBwagggPXMIID0wIBADCCA8wGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMMBbsGzlz9AIOl1NKAgEQgIIDnTVV8rPvZOJ1FU7OOHlmjO32rJ091T_ekg8
N2  - 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.
ER  -

PROKOPH, N., N.A. PROBST, L.C. LEE, J.M. MONAHAN, J.D. MATTHEWS, H.C. LIANG, K. BAHNSEN, I.A. MONTES-MOJARRO, E. KARACA-ATABAY, G.G. SHARMA, V. MALIK, H. LAROSE, S.D. FORDE, S.P. DUCRAY, Cosimo LOBELLO, Q. WANG, S.L. LUAN, Šárka POSPÍŠILOVÁ, C. GAMBACORTI-PASSERINI, G.A.A. BURKE, S. PERVEZ, A. ATTARBASCHI, A. JANIKOVA, H. PACQUEMENT, J. LANDMAN-PARKER, A. LAMBILLIOTTE, G. SCHLEIERMACHER, W. KLAPPER, R. JAUCH, W. WOESSMANN, G. VASSAL, L. KENNER, O. MERKEL, L. MOLOGNI, R. CHIARLE, L. BRUGIERES, B. GEOERGER, I. BARBIERI and Suzanne Dawn TURNER. IL10RA modulates crizotinib sensitivity in NPM1-ALK(+) anaplastic large cell lymphoma. \textit{Blood}. Washington DC, USA: American Society of Hematology, 2020, vol.~136, No~14, p.~1657-1669. ISSN~0006-4971. Available from: https://dx.doi.org/10.1182/blood.2019003793.

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