Distinct Chemokine Receptor Expression Profiles in De Novo DLBCL, Transformed Follicular Lymphoma, Richter's Trans-Formed DLBCL and Germinal Center B-Cells

Barbara Uhl; Katharina T. Prochazka; Katrin Pansy; Kerstin Wenzl; Johanna Strobl; Claudia Baumgartner; Marta M. Szmyra; James E. Waha; Axel Wolf; Peter V. Tomazic; Elisabeth Steinbauer; Maria Steinwender; Sabine Friedl; Marc Weniger; Ralf Küppers; Martin Pichler; Hildegard T. Greinix; Georg Stary; Alan G. Ramsay; Benedetta Apollonio; Julia Feichtinger; Christine Beham-Schmid; Peter Neumeister; Alexander J. Deutsch

doi:10.3390/ijms23147874

Distinct Chemokine Receptor Expression Profiles in De Novo DLBCL, Transformed Follicular Lymphoma, Richter's Trans-Formed DLBCL and Germinal Center B-Cells

Barbara Uhl, Katharina T. Prochazka, Katrin Pansy, Kerstin Wenzl, Johanna Strobl, Claudia Baumgartner, Marta M. Szmyra, James E. Waha, Axel Wolf, Peter V. Tomazic, Elisabeth Steinbauer, Maria Steinwender, Sabine Friedl, Marc Weniger, Ralf Küppers, Martin Pichler, Hildegard T. Greinix, Georg Stary, Alan G. Ramsay, Benedetta ApollonioJulia Feichtinger, Christine Beham-Schmid, Peter Neumeister, Alexander J. Deutsch

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Abstract

Chemokine receptors and their ligands have been identified as playing an important role in the development of diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, and Richter syndrome (RS). Our aim was to investigate the different expression profiles in de novo DLBCL, transformed follicular lymphoma (tFL), and RS. Here, we profiled the mRNA expression levels of 18 chemokine receptors (CCR1-CCR9, CXCR1-CXCR7, CX3CR1 and XCR1) using RQ-PCR, as well as immunohistochemistry of seven chemokine receptors (CCR1, CCR4-CCR8 and CXCR2) in RS, de novo DLBCL, and tFL biopsy-derived tissues. Tonsil-derived germinal center B-cells (GC-B) served as non-neoplastic controls. The chemokine receptor expression profiles of de novo DLBCL and tFL substantially differed from those of GC-B, with at least 5-fold higher expression of 15 out of the 18 investigated chemokine receptors (CCR1-CCR9, CXCR1, CXCR2, CXCR6, CXCR7, CX3CR1 and XCR1) in these lymphoma subtypes. Interestingly, the de novo DLBCL and tFL exhibited at least 22-fold higher expression of CCR1, CCR5, CCR8, and CXCR6 compared with RS, whereas no significant difference in chemokine receptor expression profile was detected when comparing de novo DLBCL with tFL. Furthermore, in de novo DLBCL and tFLs, a high expression of CCR7 was associated with a poor overall survival in our study cohort, as well as in an independent patient cohort. Our data indicate that the chemokine receptor expression profile of RS differs substantially from that of de novo DLBCL and tFL. Thus, these multiple dysregulated chemokine receptors could represent novel clinical markers as diagnostic and prognostic tools. Moreover, this study highlights the relevance of chemokine signaling crosstalk in the tumor microenvironment of aggressive lymphomas.

Original language	English
Article number	7874
Journal	International Journal of Molecular Sciences
Volume	23
Issue number	14
DOIs	https://doi.org/10.3390/ijms23147874
Publication status	Published - 17 Jul 2022

Keywords

CCL19
CCL21
CCR7
chemokine receptors
diffuse large B-cell lymphoma
Richter syndrome
transformed follicular lymphoma

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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istinct Chemokine Receptor Expression_UHL_2022_GOLD VoR (CC BY)Final published version, 4.08 MBLicence: CC BY

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Uhl, B., Prochazka, K. T., Pansy, K., Wenzl, K., Strobl, J., Baumgartner, C., Szmyra, M. M., Waha, J. E., Wolf, A., Tomazic, P. V., Steinbauer, E., Steinwender, M., Friedl, S., Weniger, M., Küppers, R., Pichler, M., Greinix, H. T., Stary, G., Ramsay, A. G., ... Deutsch, A. J. (2022). Distinct Chemokine Receptor Expression Profiles in De Novo DLBCL, Transformed Follicular Lymphoma, Richter's Trans-Formed DLBCL and Germinal Center B-Cells. International Journal of Molecular Sciences, 23(14), Article 7874. https://doi.org/10.3390/ijms23147874

@article{a9e4c669bce941dbbf33975bfc1a038a,

title = "Distinct Chemokine Receptor Expression Profiles in De Novo DLBCL, Transformed Follicular Lymphoma, Richter's Trans-Formed DLBCL and Germinal Center B-Cells",

abstract = "Chemokine receptors and their ligands have been identified as playing an important role in the development of diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, and Richter syndrome (RS). Our aim was to investigate the different expression profiles in de novo DLBCL, transformed follicular lymphoma (tFL), and RS. Here, we profiled the mRNA expression levels of 18 chemokine receptors (CCR1-CCR9, CXCR1-CXCR7, CX3CR1 and XCR1) using RQ-PCR, as well as immunohistochemistry of seven chemokine receptors (CCR1, CCR4-CCR8 and CXCR2) in RS, de novo DLBCL, and tFL biopsy-derived tissues. Tonsil-derived germinal center B-cells (GC-B) served as non-neoplastic controls. The chemokine receptor expression profiles of de novo DLBCL and tFL substantially differed from those of GC-B, with at least 5-fold higher expression of 15 out of the 18 investigated chemokine receptors (CCR1-CCR9, CXCR1, CXCR2, CXCR6, CXCR7, CX3CR1 and XCR1) in these lymphoma subtypes. Interestingly, the de novo DLBCL and tFL exhibited at least 22-fold higher expression of CCR1, CCR5, CCR8, and CXCR6 compared with RS, whereas no significant difference in chemokine receptor expression profile was detected when comparing de novo DLBCL with tFL. Furthermore, in de novo DLBCL and tFLs, a high expression of CCR7 was associated with a poor overall survival in our study cohort, as well as in an independent patient cohort. Our data indicate that the chemokine receptor expression profile of RS differs substantially from that of de novo DLBCL and tFL. Thus, these multiple dysregulated chemokine receptors could represent novel clinical markers as diagnostic and prognostic tools. Moreover, this study highlights the relevance of chemokine signaling crosstalk in the tumor microenvironment of aggressive lymphomas.",

keywords = "CCL19, CCL21, CCR7, chemokine receptors, diffuse large B-cell lymphoma, Richter syndrome, transformed follicular lymphoma",

author = "Barbara Uhl and Prochazka, {Katharina T.} and Katrin Pansy and Kerstin Wenzl and Johanna Strobl and Claudia Baumgartner and Szmyra, {Marta M.} and Waha, {James E.} and Axel Wolf and Tomazic, {Peter V.} and Elisabeth Steinbauer and Maria Steinwender and Sabine Friedl and Marc Weniger and Ralf K{\"u}ppers and Martin Pichler and Greinix, {Hildegard T.} and Georg Stary and Ramsay, {Alan G.} and Benedetta Apollonio and Julia Feichtinger and Christine Beham-Schmid and Peter Neumeister and Deutsch, {Alexander J.}",

note = "Funding Information: B.U. was supported by a research grant of the Austrian Society of Hematology and Medical Oncology (OeGHO). K.P. was supported by a grant of the DOC Fellowship Programme of the Austrian Academy of Sciences (award 25690) and by a research grant of the OeGHO. J.F. was supported by the Austrian Science Fund (FWF): T923-B26 and by a research grant of MEFOgraz. A.J.D. was supported by the START-Funding-Program of the Medical University of Graz, by a research grant of the MEFOgraz and by research grants of the OeGHO (clinical, translational and ASHO research grant). G.S. was supported by the Vienna Science and Technology Fund (award LS18-058). J.S. was supported by a DOC Fellowship of the Austrian Academy of Sciences. Publisher Copyright: {\textcopyright} 2022 by the authors.",

year = "2022",

month = jul,

day = "17",

doi = "10.3390/ijms23147874",

language = "English",

volume = "23",

journal = "International Journal of Molecular Sciences",

issn = "1661-6596",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "14",

}

Uhl, B, Prochazka, KT, Pansy, K, Wenzl, K, Strobl, J, Baumgartner, C, Szmyra, MM, Waha, JE, Wolf, A, Tomazic, PV, Steinbauer, E, Steinwender, M, Friedl, S, Weniger, M, Küppers, R, Pichler, M, Greinix, HT, Stary, G, Ramsay, AG , Apollonio, B, Feichtinger, J, Beham-Schmid, C, Neumeister, P & Deutsch, AJ 2022, 'Distinct Chemokine Receptor Expression Profiles in De Novo DLBCL, Transformed Follicular Lymphoma, Richter's Trans-Formed DLBCL and Germinal Center B-Cells', International Journal of Molecular Sciences, vol. 23, no. 14, 7874. https://doi.org/10.3390/ijms23147874

Distinct Chemokine Receptor Expression Profiles in De Novo DLBCL, Transformed Follicular Lymphoma, Richter's Trans-Formed DLBCL and Germinal Center B-Cells. / Uhl, Barbara; Prochazka, Katharina T.; Pansy, Katrin et al.
In: International Journal of Molecular Sciences, Vol. 23, No. 14, 7874, 17.07.2022.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Distinct Chemokine Receptor Expression Profiles in De Novo DLBCL, Transformed Follicular Lymphoma, Richter's Trans-Formed DLBCL and Germinal Center B-Cells

AU - Uhl, Barbara

AU - Prochazka, Katharina T.

AU - Pansy, Katrin

AU - Wenzl, Kerstin

AU - Strobl, Johanna

AU - Baumgartner, Claudia

AU - Szmyra, Marta M.

AU - Waha, James E.

AU - Wolf, Axel

AU - Tomazic, Peter V.

AU - Steinbauer, Elisabeth

AU - Steinwender, Maria

AU - Friedl, Sabine

AU - Weniger, Marc

AU - Küppers, Ralf

AU - Pichler, Martin

AU - Greinix, Hildegard T.

AU - Stary, Georg

AU - Ramsay, Alan G.

AU - Apollonio, Benedetta

AU - Feichtinger, Julia

AU - Beham-Schmid, Christine

AU - Neumeister, Peter

AU - Deutsch, Alexander J.

N1 - Funding Information: B.U. was supported by a research grant of the Austrian Society of Hematology and Medical Oncology (OeGHO). K.P. was supported by a grant of the DOC Fellowship Programme of the Austrian Academy of Sciences (award 25690) and by a research grant of the OeGHO. J.F. was supported by the Austrian Science Fund (FWF): T923-B26 and by a research grant of MEFOgraz. A.J.D. was supported by the START-Funding-Program of the Medical University of Graz, by a research grant of the MEFOgraz and by research grants of the OeGHO (clinical, translational and ASHO research grant). G.S. was supported by the Vienna Science and Technology Fund (award LS18-058). J.S. was supported by a DOC Fellowship of the Austrian Academy of Sciences. Publisher Copyright: © 2022 by the authors.

PY - 2022/7/17

Y1 - 2022/7/17

N2 - Chemokine receptors and their ligands have been identified as playing an important role in the development of diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, and Richter syndrome (RS). Our aim was to investigate the different expression profiles in de novo DLBCL, transformed follicular lymphoma (tFL), and RS. Here, we profiled the mRNA expression levels of 18 chemokine receptors (CCR1-CCR9, CXCR1-CXCR7, CX3CR1 and XCR1) using RQ-PCR, as well as immunohistochemistry of seven chemokine receptors (CCR1, CCR4-CCR8 and CXCR2) in RS, de novo DLBCL, and tFL biopsy-derived tissues. Tonsil-derived germinal center B-cells (GC-B) served as non-neoplastic controls. The chemokine receptor expression profiles of de novo DLBCL and tFL substantially differed from those of GC-B, with at least 5-fold higher expression of 15 out of the 18 investigated chemokine receptors (CCR1-CCR9, CXCR1, CXCR2, CXCR6, CXCR7, CX3CR1 and XCR1) in these lymphoma subtypes. Interestingly, the de novo DLBCL and tFL exhibited at least 22-fold higher expression of CCR1, CCR5, CCR8, and CXCR6 compared with RS, whereas no significant difference in chemokine receptor expression profile was detected when comparing de novo DLBCL with tFL. Furthermore, in de novo DLBCL and tFLs, a high expression of CCR7 was associated with a poor overall survival in our study cohort, as well as in an independent patient cohort. Our data indicate that the chemokine receptor expression profile of RS differs substantially from that of de novo DLBCL and tFL. Thus, these multiple dysregulated chemokine receptors could represent novel clinical markers as diagnostic and prognostic tools. Moreover, this study highlights the relevance of chemokine signaling crosstalk in the tumor microenvironment of aggressive lymphomas.

AB - Chemokine receptors and their ligands have been identified as playing an important role in the development of diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, and Richter syndrome (RS). Our aim was to investigate the different expression profiles in de novo DLBCL, transformed follicular lymphoma (tFL), and RS. Here, we profiled the mRNA expression levels of 18 chemokine receptors (CCR1-CCR9, CXCR1-CXCR7, CX3CR1 and XCR1) using RQ-PCR, as well as immunohistochemistry of seven chemokine receptors (CCR1, CCR4-CCR8 and CXCR2) in RS, de novo DLBCL, and tFL biopsy-derived tissues. Tonsil-derived germinal center B-cells (GC-B) served as non-neoplastic controls. The chemokine receptor expression profiles of de novo DLBCL and tFL substantially differed from those of GC-B, with at least 5-fold higher expression of 15 out of the 18 investigated chemokine receptors (CCR1-CCR9, CXCR1, CXCR2, CXCR6, CXCR7, CX3CR1 and XCR1) in these lymphoma subtypes. Interestingly, the de novo DLBCL and tFL exhibited at least 22-fold higher expression of CCR1, CCR5, CCR8, and CXCR6 compared with RS, whereas no significant difference in chemokine receptor expression profile was detected when comparing de novo DLBCL with tFL. Furthermore, in de novo DLBCL and tFLs, a high expression of CCR7 was associated with a poor overall survival in our study cohort, as well as in an independent patient cohort. Our data indicate that the chemokine receptor expression profile of RS differs substantially from that of de novo DLBCL and tFL. Thus, these multiple dysregulated chemokine receptors could represent novel clinical markers as diagnostic and prognostic tools. Moreover, this study highlights the relevance of chemokine signaling crosstalk in the tumor microenvironment of aggressive lymphomas.

KW - CCL19

KW - CCL21

KW - CCR7

KW - chemokine receptors

KW - diffuse large B-cell lymphoma

KW - Richter syndrome

KW - transformed follicular lymphoma

UR - http://www.scopus.com/inward/record.url?scp=85135126858&partnerID=8YFLogxK

U2 - 10.3390/ijms23147874

DO - 10.3390/ijms23147874

M3 - Article

C2 - 35887224

AN - SCOPUS:85135126858

SN - 1661-6596

VL - 23

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

IS - 14

M1 - 7874

ER -

Distinct Chemokine Receptor Expression Profiles in De Novo DLBCL, Transformed Follicular Lymphoma, Richter's Trans-Formed DLBCL and Germinal Center B-Cells

Abstract

Keywords

UN SDGs

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