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The AP-1-BATF and -BATF3 module is essential for growth, survival and TH17/ILC3 skewing of anaplastic large cell lymphoma

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The AP-1-BATF and -BATF3 module is essential for growth, survival and TH17/ILC3 skewing of anaplastic large cell lymphoma. / Schleussner, Nikolai; Merkel, Olaf; Costanza, Mariantonia; Liang, Huan-Chang; Hummel, Franziska; Romagnani, Chiara; Durek, Pawel; Anagnostopoulos, Ioannis; Hummel, Michael; Jöhrens, Korinna; Niedobitek, Antonia; Griffin, Patrick R; Piva, Roberto; Sczakiel, Henrike L; Woessmann, Wilhelm; Damm-Welk, Christine; Hinze, Christian; Stoiber, Dagmar; Gillissen, Bernd; Turner, Suzanne D; Kaergel, Eva; von Hoff, Linda; Grau, Michael; Lenz, Georg; Dörken, Bernd; Scheidereit, Claus; Kenner, Lukas; Janz, Martin; Mathas, Stephan.

In: LEUKEMIA, Vol. 32, No. 9, 09.2018, p. 1994-2007.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Schleussner, N, Merkel, O, Costanza, M, Liang, H-C, Hummel, F, Romagnani, C, Durek, P, Anagnostopoulos, I, Hummel, M, Jöhrens, K, Niedobitek, A, Griffin, PR, Piva, R, Sczakiel, HL, Woessmann, W, Damm-Welk, C, Hinze, C, Stoiber, D, Gillissen, B, Turner, SD, Kaergel, E, von Hoff, L, Grau, M, Lenz, G, Dörken, B, Scheidereit, C, Kenner, L, Janz, M & Mathas, S 2018, 'The AP-1-BATF and -BATF3 module is essential for growth, survival and TH17/ILC3 skewing of anaplastic large cell lymphoma', LEUKEMIA, vol. 32, no. 9, pp. 1994-2007. https://doi.org/10.1038/s41375-018-0045-9

APA

Schleussner, N., Merkel, O., Costanza, M., Liang, H-C., Hummel, F., Romagnani, C., Durek, P., Anagnostopoulos, I., Hummel, M., Jöhrens, K., Niedobitek, A., Griffin, P. R., Piva, R., Sczakiel, H. L., Woessmann, W., Damm-Welk, C., Hinze, C., Stoiber, D., Gillissen, B., ... Mathas, S. (2018). The AP-1-BATF and -BATF3 module is essential for growth, survival and TH17/ILC3 skewing of anaplastic large cell lymphoma. LEUKEMIA, 32(9), 1994-2007. https://doi.org/10.1038/s41375-018-0045-9

Vancouver

Schleussner N, Merkel O, Costanza M, Liang H-C, Hummel F, Romagnani C et al. The AP-1-BATF and -BATF3 module is essential for growth, survival and TH17/ILC3 skewing of anaplastic large cell lymphoma. LEUKEMIA. 2018 Sep;32(9):1994-2007. https://doi.org/10.1038/s41375-018-0045-9

Bibtex

@article{1abcbc65c0ab4f49a0c626dd84cab0db,
title = "The AP-1-BATF and -BATF3 module is essential for growth, survival and TH17/ILC3 skewing of anaplastic large cell lymphoma",
abstract = "Transcription factor AP-1 is constitutively activated and IRF4 drives growth and survival in ALK+ and ALK- anaplastic large cell lymphoma (ALCL). Here we demonstrate high-level BATF and BATF3 expression in ALCL. Both BATFs bind classical AP-1 motifs and interact with in ALCL deregulated AP-1 factors. Together with IRF4, they co-occupy AP-1-IRF composite elements, differentiating ALCL from non-ALCL. Gene-specific inactivation of BATFs, or global AP-1 inhibition results in ALCL growth retardation and/or cell death in vitro and in vivo. Furthermore, the AP-1-BATF module establishes TH17/group 3 innate lymphoid cells (ILC3)-associated gene expression in ALCL cells, including marker genes such as AHR, IL17F, IL22, IL26, IL23R and RORγt. Elevated IL-17A and IL-17F levels were detected in a subset of children and adolescents with ALK+ ALCL. Furthermore, a comprehensive analysis of primary lymphoma data confirms TH17-, and in particular ILC3-skewing in ALCL compared with PTCL. Finally, pharmacological inhibition of RORC as single treatment leads to cell death in ALCL cell lines and, in combination with the ALK inhibitor crizotinib, enforces death induction in ALK+ ALCL. Our data highlight the crucial role of AP-1/BATFs in ALCL and lead to the concept that some ALCL might originate from ILC3.",
keywords = "Journal Article",
author = "Nikolai Schleussner and Olaf Merkel and Mariantonia Costanza and Huan-Chang Liang and Franziska Hummel and Chiara Romagnani and Pawel Durek and Ioannis Anagnostopoulos and Michael Hummel and Korinna J{\"o}hrens and Antonia Niedobitek and Griffin, {Patrick R} and Roberto Piva and Sczakiel, {Henrike L} and Wilhelm Woessmann and Christine Damm-Welk and Christian Hinze and Dagmar Stoiber and Bernd Gillissen and Turner, {Suzanne D} and Eva Kaergel and {von Hoff}, Linda and Michael Grau and Georg Lenz and Bernd D{\"o}rken and Claus Scheidereit and Lukas Kenner and Martin Janz and Stephan Mathas",
year = "2018",
month = sep,
doi = "10.1038/s41375-018-0045-9",
language = "English",
volume = "32",
pages = "1994--2007",
journal = "LEUKEMIA",
issn = "0887-6924",
publisher = "NATURE PUBLISHING GROUP",
number = "9",

}

RIS

TY - JOUR

T1 - The AP-1-BATF and -BATF3 module is essential for growth, survival and TH17/ILC3 skewing of anaplastic large cell lymphoma

AU - Schleussner, Nikolai

AU - Merkel, Olaf

AU - Costanza, Mariantonia

AU - Liang, Huan-Chang

AU - Hummel, Franziska

AU - Romagnani, Chiara

AU - Durek, Pawel

AU - Anagnostopoulos, Ioannis

AU - Hummel, Michael

AU - Jöhrens, Korinna

AU - Niedobitek, Antonia

AU - Griffin, Patrick R

AU - Piva, Roberto

AU - Sczakiel, Henrike L

AU - Woessmann, Wilhelm

AU - Damm-Welk, Christine

AU - Hinze, Christian

AU - Stoiber, Dagmar

AU - Gillissen, Bernd

AU - Turner, Suzanne D

AU - Kaergel, Eva

AU - von Hoff, Linda

AU - Grau, Michael

AU - Lenz, Georg

AU - Dörken, Bernd

AU - Scheidereit, Claus

AU - Kenner, Lukas

AU - Janz, Martin

AU - Mathas, Stephan

PY - 2018/9

Y1 - 2018/9

N2 - Transcription factor AP-1 is constitutively activated and IRF4 drives growth and survival in ALK+ and ALK- anaplastic large cell lymphoma (ALCL). Here we demonstrate high-level BATF and BATF3 expression in ALCL. Both BATFs bind classical AP-1 motifs and interact with in ALCL deregulated AP-1 factors. Together with IRF4, they co-occupy AP-1-IRF composite elements, differentiating ALCL from non-ALCL. Gene-specific inactivation of BATFs, or global AP-1 inhibition results in ALCL growth retardation and/or cell death in vitro and in vivo. Furthermore, the AP-1-BATF module establishes TH17/group 3 innate lymphoid cells (ILC3)-associated gene expression in ALCL cells, including marker genes such as AHR, IL17F, IL22, IL26, IL23R and RORγt. Elevated IL-17A and IL-17F levels were detected in a subset of children and adolescents with ALK+ ALCL. Furthermore, a comprehensive analysis of primary lymphoma data confirms TH17-, and in particular ILC3-skewing in ALCL compared with PTCL. Finally, pharmacological inhibition of RORC as single treatment leads to cell death in ALCL cell lines and, in combination with the ALK inhibitor crizotinib, enforces death induction in ALK+ ALCL. Our data highlight the crucial role of AP-1/BATFs in ALCL and lead to the concept that some ALCL might originate from ILC3.

AB - Transcription factor AP-1 is constitutively activated and IRF4 drives growth and survival in ALK+ and ALK- anaplastic large cell lymphoma (ALCL). Here we demonstrate high-level BATF and BATF3 expression in ALCL. Both BATFs bind classical AP-1 motifs and interact with in ALCL deregulated AP-1 factors. Together with IRF4, they co-occupy AP-1-IRF composite elements, differentiating ALCL from non-ALCL. Gene-specific inactivation of BATFs, or global AP-1 inhibition results in ALCL growth retardation and/or cell death in vitro and in vivo. Furthermore, the AP-1-BATF module establishes TH17/group 3 innate lymphoid cells (ILC3)-associated gene expression in ALCL cells, including marker genes such as AHR, IL17F, IL22, IL26, IL23R and RORγt. Elevated IL-17A and IL-17F levels were detected in a subset of children and adolescents with ALK+ ALCL. Furthermore, a comprehensive analysis of primary lymphoma data confirms TH17-, and in particular ILC3-skewing in ALCL compared with PTCL. Finally, pharmacological inhibition of RORC as single treatment leads to cell death in ALCL cell lines and, in combination with the ALK inhibitor crizotinib, enforces death induction in ALK+ ALCL. Our data highlight the crucial role of AP-1/BATFs in ALCL and lead to the concept that some ALCL might originate from ILC3.

KW - Journal Article

U2 - 10.1038/s41375-018-0045-9

DO - 10.1038/s41375-018-0045-9

M3 - SCORING: Journal article

C2 - 29588546

VL - 32

SP - 1994

EP - 2007

JO - LEUKEMIA

JF - LEUKEMIA

SN - 0887-6924

IS - 9

ER -