Stem cell characteristics promote aggressiveness of diffuse large B-cell lymphoma

Abstract Diffuse large B-cell lymphoma (DLBCL) may present initially in bone marrow, liver and spleen without any lymphadenopathy (referred to as BLS-type DLBCL), which is aggressive and frequently associated with hemophagocytic syndrome. Its tumorigenesis and molecular mechanisms warrant clarificat...

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Autores principales:	Kung-Chao Chang, Ruo-Yu Chen, Yu-Chu Wang, Liang-Yi Hung, L. Jeffrey Medeiros, Ya-Ping Chen, Tsai-Yun Chen, Jui-Chu Yang, Po-Min Chiang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/68dd808b9c9d4c91a9092e920931f2c1
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spelling	oai:doaj.org-article:68dd808b9c9d4c91a9092e920931f2c12021-12-02T12:34:17ZStem cell characteristics promote aggressiveness of diffuse large B-cell lymphoma10.1038/s41598-020-78508-72045-2322https://doaj.org/article/68dd808b9c9d4c91a9092e920931f2c12020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78508-7https://doaj.org/toc/2045-2322Abstract Diffuse large B-cell lymphoma (DLBCL) may present initially in bone marrow, liver and spleen without any lymphadenopathy (referred to as BLS-type DLBCL), which is aggressive and frequently associated with hemophagocytic syndrome. Its tumorigenesis and molecular mechanisms warrant clarification. By gene microarray profiling with bioinformatics analysis, we found higher expression of the stem cell markers HOXA9 and NANOG, as well as BMP8B, CCR6 and S100A8 in BLS-type than conventional DLBCL. We further validated expression of these markers in a large cohort of DLBCL including BLS-type cases and found that expression of HOXA9 and NANOG correlated with inferior outcome and poor prognostic parameters. Functional studies with gene-overexpressed and gene-silenced DLBCL cell lines showed that expression of NANOG and HOXA9 promoted cell viability and inhibited apoptosis through suppression of G2 arrest in vitro and enhanced tumor formation and hepatosplenic infiltration in a tail-vein-injected mouse model. Additionally, HOXA9-transfected tumor cells showed significantly increased soft-agar clonogenic ability and tumor sphere formation. Interestingly, B cells with higher CCR6 expression revealed a higher chemotactic migration for CCL20. Taken together, our findings support the concept that tumor or precursor cells of BLS-type DLBCL are attracted by chemotaxis and home to the bone marrow, where the microenvironment promotes the expression of stem cell characteristics and aggressiveness of tumor cells.Kung-Chao ChangRuo-Yu ChenYu-Chu WangLiang-Yi HungL. Jeffrey MedeirosYa-Ping ChenTsai-Yun ChenJui-Chu YangPo-Min ChiangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-17 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kung-Chao Chang Ruo-Yu Chen Yu-Chu Wang Liang-Yi Hung L. Jeffrey Medeiros Ya-Ping Chen Tsai-Yun Chen Jui-Chu Yang Po-Min Chiang Stem cell characteristics promote aggressiveness of diffuse large B-cell lymphoma
description	Abstract Diffuse large B-cell lymphoma (DLBCL) may present initially in bone marrow, liver and spleen without any lymphadenopathy (referred to as BLS-type DLBCL), which is aggressive and frequently associated with hemophagocytic syndrome. Its tumorigenesis and molecular mechanisms warrant clarification. By gene microarray profiling with bioinformatics analysis, we found higher expression of the stem cell markers HOXA9 and NANOG, as well as BMP8B, CCR6 and S100A8 in BLS-type than conventional DLBCL. We further validated expression of these markers in a large cohort of DLBCL including BLS-type cases and found that expression of HOXA9 and NANOG correlated with inferior outcome and poor prognostic parameters. Functional studies with gene-overexpressed and gene-silenced DLBCL cell lines showed that expression of NANOG and HOXA9 promoted cell viability and inhibited apoptosis through suppression of G2 arrest in vitro and enhanced tumor formation and hepatosplenic infiltration in a tail-vein-injected mouse model. Additionally, HOXA9-transfected tumor cells showed significantly increased soft-agar clonogenic ability and tumor sphere formation. Interestingly, B cells with higher CCR6 expression revealed a higher chemotactic migration for CCL20. Taken together, our findings support the concept that tumor or precursor cells of BLS-type DLBCL are attracted by chemotaxis and home to the bone marrow, where the microenvironment promotes the expression of stem cell characteristics and aggressiveness of tumor cells.
format	article
author	Kung-Chao Chang Ruo-Yu Chen Yu-Chu Wang Liang-Yi Hung L. Jeffrey Medeiros Ya-Ping Chen Tsai-Yun Chen Jui-Chu Yang Po-Min Chiang
author_facet	Kung-Chao Chang Ruo-Yu Chen Yu-Chu Wang Liang-Yi Hung L. Jeffrey Medeiros Ya-Ping Chen Tsai-Yun Chen Jui-Chu Yang Po-Min Chiang
author_sort	Kung-Chao Chang
title	Stem cell characteristics promote aggressiveness of diffuse large B-cell lymphoma
title_short	Stem cell characteristics promote aggressiveness of diffuse large B-cell lymphoma
title_full	Stem cell characteristics promote aggressiveness of diffuse large B-cell lymphoma
title_fullStr	Stem cell characteristics promote aggressiveness of diffuse large B-cell lymphoma
title_full_unstemmed	Stem cell characteristics promote aggressiveness of diffuse large B-cell lymphoma
title_sort	stem cell characteristics promote aggressiveness of diffuse large b-cell lymphoma
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/68dd808b9c9d4c91a9092e920931f2c1
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_version_	1718393862711410688

Stem cell characteristics promote aggressiveness of diffuse large B-cell lymphoma

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