Haploinsufficiency of Bcl11b suppresses the progression of ATM-deficient T cell lymphomas

Bcl11b is a transcription factor important for T cell development and also a tumor-suppressor gene that is hemizygously inactivated in ~10 % human T cell acute lymphoblastic leukemia (T-ALL) and several murine T-ALL models, including ATM(−/−) thymic lymphomas. Here we report that heterozygous loss o...

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Autores principales: Pinkney, Kerice A., Jiang, Wenxia, Lee, Brian J., Loredan, Denis G., Li, Chen, Bhagat, Govind, Zha, Shan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Letter to the Editor
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4518599/
https://www.ncbi.nlm.nih.gov/pubmed/26219558
http://dx.doi.org/10.1186/s13045-015-0191-8
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author Pinkney, Kerice A.
Jiang, Wenxia
Lee, Brian J.
Loredan, Denis G.
Li, Chen
Bhagat, Govind
Zha, Shan
author_facet Pinkney, Kerice A.
Jiang, Wenxia
Lee, Brian J.
Loredan, Denis G.
Li, Chen
Bhagat, Govind
Zha, Shan
author_sort Pinkney, Kerice A.
collection PubMed
description Bcl11b is a transcription factor important for T cell development and also a tumor-suppressor gene that is hemizygously inactivated in ~10 % human T cell acute lymphoblastic leukemia (T-ALL) and several murine T-ALL models, including ATM(−/−) thymic lymphomas. Here we report that heterozygous loss of Bcl11b (Bcl11b(+/−)) unexpectedly reduced lethal thymic lymphoma in ATM(−/−) mice by suppressing lymphoma progression, but not initiation. The suppression was associated with a T cell-mediated immune response in ATM(−/−)Bcl11b(+/−) mice, revealing a haploid insufficient function of Bcl11b in immune modulation against lymphoma and offering an explanation for the complex relationship between Bcl11b status with T-ALL prognosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13045-015-0191-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-45185992015-07-30 Haploinsufficiency of Bcl11b suppresses the progression of ATM-deficient T cell lymphomas Pinkney, Kerice A. Jiang, Wenxia Lee, Brian J. Loredan, Denis G. Li, Chen Bhagat, Govind Zha, Shan J Hematol Oncol Letter to the Editor Bcl11b is a transcription factor important for T cell development and also a tumor-suppressor gene that is hemizygously inactivated in ~10 % human T cell acute lymphoblastic leukemia (T-ALL) and several murine T-ALL models, including ATM(−/−) thymic lymphomas. Here we report that heterozygous loss of Bcl11b (Bcl11b(+/−)) unexpectedly reduced lethal thymic lymphoma in ATM(−/−) mice by suppressing lymphoma progression, but not initiation. The suppression was associated with a T cell-mediated immune response in ATM(−/−)Bcl11b(+/−) mice, revealing a haploid insufficient function of Bcl11b in immune modulation against lymphoma and offering an explanation for the complex relationship between Bcl11b status with T-ALL prognosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13045-015-0191-8) contains supplementary material, which is available to authorized users. BioMed Central 2015-07-30 /pmc/articles/PMC4518599/ /pubmed/26219558 http://dx.doi.org/10.1186/s13045-015-0191-8 Text en © Pinkney et al. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Letter to the Editor
Pinkney, Kerice A.
Jiang, Wenxia
Lee, Brian J.
Loredan, Denis G.
Li, Chen
Bhagat, Govind
Zha, Shan
Haploinsufficiency of Bcl11b suppresses the progression of ATM-deficient T cell lymphomas
title Haploinsufficiency of Bcl11b suppresses the progression of ATM-deficient T cell lymphomas
title_full Haploinsufficiency of Bcl11b suppresses the progression of ATM-deficient T cell lymphomas
title_fullStr Haploinsufficiency of Bcl11b suppresses the progression of ATM-deficient T cell lymphomas
title_full_unstemmed Haploinsufficiency of Bcl11b suppresses the progression of ATM-deficient T cell lymphomas
title_short Haploinsufficiency of Bcl11b suppresses the progression of ATM-deficient T cell lymphomas
title_sort haploinsufficiency of bcl11b suppresses the progression of atm-deficient t cell lymphomas
topic Letter to the Editor
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4518599/
https://www.ncbi.nlm.nih.gov/pubmed/26219558
http://dx.doi.org/10.1186/s13045-015-0191-8
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