BRG1 and NPM-ALK Are Co-Regulated in Anaplastic Large-Cell
Lymphoma; BRG1 Is a Potential Therapeutic Target in ALCL

J 2022

BRG1 and NPM-ALK Are Co-Regulated in Anaplastic Large-Cell Lymphoma; BRG1 Is a Potential Therapeutic Target in ALCL

GARLAND, Gavin D, Stephen P DUCRAY, Leila JAHANGIRI, Perla PUCCI, G.A. AMOS BURKE et. al.

Basic information

Original name

BRG1 and NPM-ALK Are Co-Regulated in Anaplastic Large-Cell Lymphoma; BRG1 Is a Potential Therapeutic Target in ALCL

Authors

Edition

CANCERS, BASEL, Mediscript Ltd. 2022, 2072-6694

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.200

RIV identification code

RIV/00216224:14740/22:00126467

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.3390/cancers14010151

UT WoS

000741380300001

Keywords in English

NPM-ALK; ALCL; Brg1

Abstract

V originále

Simple Summary T-cell lymphoma is a cancer of the immune system. One specific sub-type of T-cell lymphoma is a malignancy called anaplastic large cell lymphoma (ALCL), which is distinct from the other forms, as in general, it has a better prognosis. Research conducted to understand why ALCL develops has shown that a specific genetic event occurs, whereby a new protein is created that drives tumour growth. This protein is called nucleophosmin-anaplastic lymphoma kinase (NPM-ALK). Our research, described here, shows that NPM-ALK regulates another protein, called BRG1, to drive proliferation of tumour cells. In turn, when the gene that leads to expression of BRG1 is inactivated, the tumour cells die. These data suggest that therapeutic targeting of BRG1 might be a novel therapy for this form of cancer. Anaplastic large-cell lymphoma (ALCL) is a T-cell malignancy driven in many cases by the product of a chromosomal translocation, nucleophosmin-anaplastic lymphoma kinase (NPM-ALK). NPM-ALK activates a plethora of pathways that drive the hallmarks of cancer, largely signalling pathways normally associated with cytokine and/or T-cell receptor-induced signalling. However, NPM-ALK is also located in the nucleus and its functions in this cellular compartment for the most part remain to be determined. We show that ALCL cell lines and primary patient tumours express the transcriptional activator BRG1 in a NPM-ALK-dependent manner. NPM-ALK regulates expression of BRG1 by post-translational mechanisms dependent on its kinase activity, protecting it from proteasomal degradation. Furthermore, we show that BRG1 drives a transcriptional programme associated with cell cycle progression. In turn, inhibition of BRG1 expression with specific shRNA decreases cell viability, suggesting that it may represent a key therapeutic target for the treatment of ALCL.

Citovat

GARLAND, Gavin D, Stephen P DUCRAY, Leila JAHANGIRI, Perla PUCCI, G.A. AMOS BURKE, Jack MONAHAN, Raymond LAI, Olaf MERKEL, Ana-Iris SCHIEFER, Lukas KENNER, Andrew J BANNISTER and Suzanne Dawn TURNER. BRG1 and NPM-ALK Are Co-Regulated in Anaplastic Large-Cell Lymphoma; BRG1 Is a Potential Therapeutic Target in ALCL. CANCERS. BASEL: Mediscript Ltd., 2022, vol. 14, No 1, p. 151-165. ISSN 2072-6694. Available from: https://dx.doi.org/10.3390/cancers14010151.

@article{2212074,
   author = {Garland, Gavin D and Ducray, Stephen P and Jahangiri, Leila and Pucci, Perla and Amos Burke, G.A. and Monahan, Jack and Lai, Raymond and Merkel, Olaf and Schiefer, AnaandIris and Kenner, Lukas and Bannister, Andrew J and Turner, Suzanne Dawn},
   article_location = {BASEL},
   article_number = {1},
   doi = {http://dx.doi.org/10.3390/cancers14010151},
   keywords = {NPM-ALK; ALCL; Brg1},
   language = {eng},
   issn = {2072-6694},
   journal = {CANCERS},
   title = {BRG1 and NPM-ALK Are Co-Regulated in Anaplastic Large-Cell Lymphoma; BRG1 Is a Potential Therapeutic Target in ALCL},
   url = {https://www.mdpi.com/2072-6694/14/1/151},
   volume = {14},
   year = {2022}
}

TY  - JOUR
ID  - 2212074
AU  - Garland, Gavin D - Ducray, Stephen P - Jahangiri, Leila - Pucci, Perla - Amos Burke, G.A. - Monahan, Jack - Lai, Raymond - Merkel, Olaf - Schiefer, Ana-Iris - Kenner, Lukas - Bannister, Andrew J - Turner, Suzanne Dawn
PY  - 2022
TI  - BRG1 and NPM-ALK Are Co-Regulated in Anaplastic Large-Cell Lymphoma; BRG1 Is a Potential Therapeutic Target in ALCL
JF  - CANCERS
VL  - 14
IS  - 1
SP  - 151
EP  - 151
PB  - Mediscript Ltd.
SN  - 20726694
KW  - NPM-ALK
KW  - ALCL
KW  - Brg1
UR  - https://www.mdpi.com/2072-6694/14/1/151
N2  - Simple Summary T-cell lymphoma is a cancer of the immune system. One specific sub-type of T-cell lymphoma is a malignancy called anaplastic large cell lymphoma (ALCL), which is distinct from the other forms, as in general, it has a better prognosis. Research conducted to understand why ALCL develops has shown that a specific genetic event occurs, whereby a new protein is created that drives tumour growth. This protein is called nucleophosmin-anaplastic lymphoma kinase (NPM-ALK). Our research, described here, shows that NPM-ALK regulates another protein, called BRG1, to drive proliferation of tumour cells. In turn, when the gene that leads to expression of BRG1 is inactivated, the tumour cells die. These data suggest that therapeutic targeting of BRG1 might be a novel therapy for this form of cancer. Anaplastic large-cell lymphoma (ALCL) is a T-cell malignancy driven in many cases by the product of a chromosomal translocation, nucleophosmin-anaplastic lymphoma kinase (NPM-ALK). NPM-ALK activates a plethora of pathways that drive the hallmarks of cancer, largely signalling pathways normally associated with cytokine and/or T-cell receptor-induced signalling. However, NPM-ALK is also located in the nucleus and its functions in this cellular compartment for the most part remain to be determined. We show that ALCL cell lines and primary patient tumours express the transcriptional activator BRG1 in a NPM-ALK-dependent manner. NPM-ALK regulates expression of BRG1 by post-translational mechanisms dependent on its kinase activity, protecting it from proteasomal degradation. Furthermore, we show that BRG1 drives a transcriptional programme associated with cell cycle progression. In turn, inhibition of BRG1 expression with specific shRNA decreases cell viability, suggesting that it may represent a key therapeutic target for the treatment of ALCL.
ER  -

GARLAND, Gavin D, Stephen P DUCRAY, Leila JAHANGIRI, Perla PUCCI, G.A. AMOS BURKE, Jack MONAHAN, Raymond LAI, Olaf MERKEL, Ana-Iris SCHIEFER, Lukas KENNER, Andrew J BANNISTER and Suzanne Dawn TURNER. BRG1 and NPM-ALK Are Co-Regulated in Anaplastic Large-Cell Lymphoma; BRG1 Is a Potential Therapeutic Target in ALCL. \textit{CANCERS}. BASEL: Mediscript Ltd., 2022, vol.~14, No~1, p.~151-165. ISSN~2072-6694. Available from: https://dx.doi.org/10.3390/cancers14010151.

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