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Molecular profiling reveals immunogenic cues in anaplastic large cell lymphomas with DUSP22 rearrangements

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Harvard

Luchtel, RA, Dasari, S, Oishi, N, Pedersen, MB, Hu, G, Rech, KL, Ketterling, RP, Sidhu, J, Wang, X, Katoh, R, Dogan, A, Kip, NS, Cunningham, JM, Sun, Z, Baheti, S, Porcher, JC, Said, JW, Jiang, L, Hamilton-Dutoit, SJ, Møller, MB, Nørgaard, P, Bennani, NN, Chng, W-J, Huang, G, Link, BK, Facchetti, F, Cerhan, JR, d'Amore, F, Ansell, SM & Feldman, AL 2018, 'Molecular profiling reveals immunogenic cues in anaplastic large cell lymphomas with DUSP22 rearrangements' Blood, bind 132, nr. 13, s. 1386-1398. https://doi.org/10.1182/blood-2018-03-838524

APA

Luchtel, R. A., Dasari, S., Oishi, N., Pedersen, M. B., Hu, G., Rech, K. L., ... Feldman, A. L. (2018). Molecular profiling reveals immunogenic cues in anaplastic large cell lymphomas with DUSP22 rearrangements. Blood, 132(13), 1386-1398. https://doi.org/10.1182/blood-2018-03-838524

CBE

Luchtel RA, Dasari S, Oishi N, Pedersen MB, Hu G, Rech KL, Ketterling RP, Sidhu J, Wang X, Katoh R, Dogan A, Kip NS, Cunningham JM, Sun Z, Baheti S, Porcher JC, Said JW, Jiang L, Hamilton-Dutoit SJ, Møller MB, Nørgaard P, Bennani NN, Chng W-J, Huang G, Link BK, Facchetti F, Cerhan JR, d'Amore F, Ansell SM, Feldman AL. 2018. Molecular profiling reveals immunogenic cues in anaplastic large cell lymphomas with DUSP22 rearrangements. Blood. 132(13):1386-1398. https://doi.org/10.1182/blood-2018-03-838524

MLA

Vancouver

Author

Luchtel, Rebecca A ; Dasari, Surendra ; Oishi, Naoki ; Pedersen, Martin Bjerregård ; Hu, Guangzhen ; Rech, Karen L ; Ketterling, Rhett P ; Sidhu, Jagmohan ; Wang, Xueju ; Katoh, Ryohei ; Dogan, Ahmet ; Kip, N Sertac ; Cunningham, Julie M ; Sun, Zhifu ; Baheti, Saurabh ; Porcher, Julie C ; Said, Jonathan W ; Jiang, Liuyan ; Hamilton-Dutoit, Stephen Jacques ; Møller, Michael Boe ; Nørgaard, Peter ; Bennani, N Nora ; Chng, Wee-Joo ; Huang, Gaofeng ; Link, Brian K ; Facchetti, Fabio ; Cerhan, James R ; d'Amore, Francesco ; Ansell, Stephen M ; Feldman, Andrew L. / Molecular profiling reveals immunogenic cues in anaplastic large cell lymphomas with DUSP22 rearrangements. I: Blood. 2018 ; Bind 132, Nr. 13. s. 1386-1398.

Bibtex

@article{33d7269f66504335b496f6b8e397ac55,
title = "Molecular profiling reveals immunogenic cues in anaplastic large cell lymphomas with DUSP22 rearrangements",
abstract = "Anaplastic large cell lymphomas (ALCLs) are CD30-positive T-cell non-Hodgkin lymphomas broadly segregated into ALK-positive and ALK-negative types. Although ALK-positive ALCLs consistently bear rearrangements of the ALK tyrosine kinase gene, ALK-negative ALCLs are clinically and genetically heterogeneous. About 30{\%} of ALK-negative ALCLs have rearrangements of DUSP22 and have excellent long-term outcomes with standard therapy. To better understand this group of tumors, we evaluated their molecular signature using gene expression profiling. DUSP22-rearranged ALCLs belonged to a distinct subset of ALCLs that lacked expression of genes associated with JAK-STAT3 signaling, a pathway contributing to growth in the majority of ALCLs. Reverse-phase protein array and immunohistochemical studies confirmed the lack of activated STAT3 in DUSP22-rearranged ALCLs. DUSP22-rearranged ALCLs also overexpressed immunogenic cancer-testis antigen (CTA) genes and showed marked DNA hypomethylation by reduced representation bisulfate sequencing and DNA methylation arrays. Pharmacologic DNA demethylation in ALCL cells recapitulated the overexpression of CTAs and other DUSP22 signature genes. In addition, DUSP22-rearranged ALCLs minimally expressed PD-L1 compared with other ALCLs, but showed high expression of the costimulatory gene CD58 and HLA class II. Taken together, these findings indicate that DUSP22 rearrangements define a molecularly distinct subgroup of ALCLs, and that immunogenic cues related to antigenicity, costimulatory molecule expression, and inactivity of the PD-1/PD-L1 immune checkpoint likely contribute to their favorable prognosis. More aggressive ALCLs might be pharmacologically reprogrammed to a DUSP22-like immunogenic molecular signature through the use of demethylating agents and/or immune checkpoint inhibitors.",
author = "Luchtel, {Rebecca A} and Surendra Dasari and Naoki Oishi and Pedersen, {Martin Bjerreg{\aa}rd} and Guangzhen Hu and Rech, {Karen L} and Ketterling, {Rhett P} and Jagmohan Sidhu and Xueju Wang and Ryohei Katoh and Ahmet Dogan and Kip, {N Sertac} and Cunningham, {Julie M} and Zhifu Sun and Saurabh Baheti and Porcher, {Julie C} and Said, {Jonathan W} and Liuyan Jiang and Hamilton-Dutoit, {Stephen Jacques} and M{\o}ller, {Michael Boe} and Peter N{\o}rgaard and Bennani, {N Nora} and Wee-Joo Chng and Gaofeng Huang and Link, {Brian K} and Fabio Facchetti and Cerhan, {James R} and Francesco d'Amore and Ansell, {Stephen M} and Feldman, {Andrew L}",
note = "{\circledC} 2018 by The American Society of Hematology.",
year = "2018",
month = "9",
day = "27",
doi = "10.1182/blood-2018-03-838524",
language = "English",
volume = "132",
pages = "1386--1398",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "13",

}

RIS

TY - JOUR

T1 - Molecular profiling reveals immunogenic cues in anaplastic large cell lymphomas with DUSP22 rearrangements

AU - Luchtel, Rebecca A

AU - Dasari, Surendra

AU - Oishi, Naoki

AU - Pedersen, Martin Bjerregård

AU - Hu, Guangzhen

AU - Rech, Karen L

AU - Ketterling, Rhett P

AU - Sidhu, Jagmohan

AU - Wang, Xueju

AU - Katoh, Ryohei

AU - Dogan, Ahmet

AU - Kip, N Sertac

AU - Cunningham, Julie M

AU - Sun, Zhifu

AU - Baheti, Saurabh

AU - Porcher, Julie C

AU - Said, Jonathan W

AU - Jiang, Liuyan

AU - Hamilton-Dutoit, Stephen Jacques

AU - Møller, Michael Boe

AU - Nørgaard, Peter

AU - Bennani, N Nora

AU - Chng, Wee-Joo

AU - Huang, Gaofeng

AU - Link, Brian K

AU - Facchetti, Fabio

AU - Cerhan, James R

AU - d'Amore, Francesco

AU - Ansell, Stephen M

AU - Feldman, Andrew L

N1 - © 2018 by The American Society of Hematology.

PY - 2018/9/27

Y1 - 2018/9/27

N2 - Anaplastic large cell lymphomas (ALCLs) are CD30-positive T-cell non-Hodgkin lymphomas broadly segregated into ALK-positive and ALK-negative types. Although ALK-positive ALCLs consistently bear rearrangements of the ALK tyrosine kinase gene, ALK-negative ALCLs are clinically and genetically heterogeneous. About 30% of ALK-negative ALCLs have rearrangements of DUSP22 and have excellent long-term outcomes with standard therapy. To better understand this group of tumors, we evaluated their molecular signature using gene expression profiling. DUSP22-rearranged ALCLs belonged to a distinct subset of ALCLs that lacked expression of genes associated with JAK-STAT3 signaling, a pathway contributing to growth in the majority of ALCLs. Reverse-phase protein array and immunohistochemical studies confirmed the lack of activated STAT3 in DUSP22-rearranged ALCLs. DUSP22-rearranged ALCLs also overexpressed immunogenic cancer-testis antigen (CTA) genes and showed marked DNA hypomethylation by reduced representation bisulfate sequencing and DNA methylation arrays. Pharmacologic DNA demethylation in ALCL cells recapitulated the overexpression of CTAs and other DUSP22 signature genes. In addition, DUSP22-rearranged ALCLs minimally expressed PD-L1 compared with other ALCLs, but showed high expression of the costimulatory gene CD58 and HLA class II. Taken together, these findings indicate that DUSP22 rearrangements define a molecularly distinct subgroup of ALCLs, and that immunogenic cues related to antigenicity, costimulatory molecule expression, and inactivity of the PD-1/PD-L1 immune checkpoint likely contribute to their favorable prognosis. More aggressive ALCLs might be pharmacologically reprogrammed to a DUSP22-like immunogenic molecular signature through the use of demethylating agents and/or immune checkpoint inhibitors.

AB - Anaplastic large cell lymphomas (ALCLs) are CD30-positive T-cell non-Hodgkin lymphomas broadly segregated into ALK-positive and ALK-negative types. Although ALK-positive ALCLs consistently bear rearrangements of the ALK tyrosine kinase gene, ALK-negative ALCLs are clinically and genetically heterogeneous. About 30% of ALK-negative ALCLs have rearrangements of DUSP22 and have excellent long-term outcomes with standard therapy. To better understand this group of tumors, we evaluated their molecular signature using gene expression profiling. DUSP22-rearranged ALCLs belonged to a distinct subset of ALCLs that lacked expression of genes associated with JAK-STAT3 signaling, a pathway contributing to growth in the majority of ALCLs. Reverse-phase protein array and immunohistochemical studies confirmed the lack of activated STAT3 in DUSP22-rearranged ALCLs. DUSP22-rearranged ALCLs also overexpressed immunogenic cancer-testis antigen (CTA) genes and showed marked DNA hypomethylation by reduced representation bisulfate sequencing and DNA methylation arrays. Pharmacologic DNA demethylation in ALCL cells recapitulated the overexpression of CTAs and other DUSP22 signature genes. In addition, DUSP22-rearranged ALCLs minimally expressed PD-L1 compared with other ALCLs, but showed high expression of the costimulatory gene CD58 and HLA class II. Taken together, these findings indicate that DUSP22 rearrangements define a molecularly distinct subgroup of ALCLs, and that immunogenic cues related to antigenicity, costimulatory molecule expression, and inactivity of the PD-1/PD-L1 immune checkpoint likely contribute to their favorable prognosis. More aggressive ALCLs might be pharmacologically reprogrammed to a DUSP22-like immunogenic molecular signature through the use of demethylating agents and/or immune checkpoint inhibitors.

U2 - 10.1182/blood-2018-03-838524

DO - 10.1182/blood-2018-03-838524

M3 - Journal article

VL - 132

SP - 1386

EP - 1398

JO - Blood

JF - Blood

SN - 0006-4971

IS - 13

ER -

ID: 56605592