Cargando…
The role of the atypical chemokine receptor CCRL2 in myelodysplastic syndrome and secondary acute myeloid leukemia
The identification of new pathways supporting the myelodysplastic syndrome (MDS) primitive cells growth is required to develop targeted therapies. Within myeloid malignancies, men have worse outcomes than women, suggesting male sex hormone–driven effects in malignant hematopoiesis. Androgen receptor...
Autores principales: | , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8856621/ https://www.ncbi.nlm.nih.gov/pubmed/35179961 http://dx.doi.org/10.1126/sciadv.abl8952 |
_version_ | 1784653885661511680 |
---|---|
author | Karantanos, Theodoros Teodorescu, Patric Perkins, Brandy Christodoulou, Ilias Esteb, Christopher Varadhan, Ravi Helmenstine, Eric Rajkhowa, Trivikram Paun, Bogdan C. Bonifant, Challice Dalton, W. Brian Gondek, Lukasz P. Moliterno, Alison R. Levis, Mark J. Ghiaur, Gabriel Jones, Richard J. |
author_facet | Karantanos, Theodoros Teodorescu, Patric Perkins, Brandy Christodoulou, Ilias Esteb, Christopher Varadhan, Ravi Helmenstine, Eric Rajkhowa, Trivikram Paun, Bogdan C. Bonifant, Challice Dalton, W. Brian Gondek, Lukasz P. Moliterno, Alison R. Levis, Mark J. Ghiaur, Gabriel Jones, Richard J. |
author_sort | Karantanos, Theodoros |
collection | PubMed |
description | The identification of new pathways supporting the myelodysplastic syndrome (MDS) primitive cells growth is required to develop targeted therapies. Within myeloid malignancies, men have worse outcomes than women, suggesting male sex hormone–driven effects in malignant hematopoiesis. Androgen receptor promotes the expression of five granulocyte colony-stimulating factor receptor–regulated genes. Among them, CCRL2 encodes an atypical chemokine receptor regulating cytokine signaling in granulocytes, but its role in myeloid malignancies is unknown. Our study revealed that CCRL2 is up-regulated in primitive cells from patients with MDS and secondary acute myeloid leukemia (sAML). CCRL2 knockdown suppressed MDS92 and MDS-L cell growth and clonogenicity in vitro and in vivo and decreased JAK2/STAT3/STAT5 phosphorylation. CCRL2 coprecipitated with JAK2 and potentiated JAK2-STAT interaction. Erythroleukemia cells expressing JAK2V617F showed less effect of CCRL2 knockdown, whereas fedratinib potentiated the CCRL2 knockdown effect. Conclusively, our results implicate CCRL2 as an MDS/sAML cell growth mediator, partially through JAK2/STAT signaling. |
format | Online Article Text |
id | pubmed-8856621 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-88566212022-03-04 The role of the atypical chemokine receptor CCRL2 in myelodysplastic syndrome and secondary acute myeloid leukemia Karantanos, Theodoros Teodorescu, Patric Perkins, Brandy Christodoulou, Ilias Esteb, Christopher Varadhan, Ravi Helmenstine, Eric Rajkhowa, Trivikram Paun, Bogdan C. Bonifant, Challice Dalton, W. Brian Gondek, Lukasz P. Moliterno, Alison R. Levis, Mark J. Ghiaur, Gabriel Jones, Richard J. Sci Adv Biomedicine and Life Sciences The identification of new pathways supporting the myelodysplastic syndrome (MDS) primitive cells growth is required to develop targeted therapies. Within myeloid malignancies, men have worse outcomes than women, suggesting male sex hormone–driven effects in malignant hematopoiesis. Androgen receptor promotes the expression of five granulocyte colony-stimulating factor receptor–regulated genes. Among them, CCRL2 encodes an atypical chemokine receptor regulating cytokine signaling in granulocytes, but its role in myeloid malignancies is unknown. Our study revealed that CCRL2 is up-regulated in primitive cells from patients with MDS and secondary acute myeloid leukemia (sAML). CCRL2 knockdown suppressed MDS92 and MDS-L cell growth and clonogenicity in vitro and in vivo and decreased JAK2/STAT3/STAT5 phosphorylation. CCRL2 coprecipitated with JAK2 and potentiated JAK2-STAT interaction. Erythroleukemia cells expressing JAK2V617F showed less effect of CCRL2 knockdown, whereas fedratinib potentiated the CCRL2 knockdown effect. Conclusively, our results implicate CCRL2 as an MDS/sAML cell growth mediator, partially through JAK2/STAT signaling. American Association for the Advancement of Science 2022-02-18 /pmc/articles/PMC8856621/ /pubmed/35179961 http://dx.doi.org/10.1126/sciadv.abl8952 Text en Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Karantanos, Theodoros Teodorescu, Patric Perkins, Brandy Christodoulou, Ilias Esteb, Christopher Varadhan, Ravi Helmenstine, Eric Rajkhowa, Trivikram Paun, Bogdan C. Bonifant, Challice Dalton, W. Brian Gondek, Lukasz P. Moliterno, Alison R. Levis, Mark J. Ghiaur, Gabriel Jones, Richard J. The role of the atypical chemokine receptor CCRL2 in myelodysplastic syndrome and secondary acute myeloid leukemia |
title | The role of the atypical chemokine receptor CCRL2 in myelodysplastic syndrome and secondary acute myeloid leukemia |
title_full | The role of the atypical chemokine receptor CCRL2 in myelodysplastic syndrome and secondary acute myeloid leukemia |
title_fullStr | The role of the atypical chemokine receptor CCRL2 in myelodysplastic syndrome and secondary acute myeloid leukemia |
title_full_unstemmed | The role of the atypical chemokine receptor CCRL2 in myelodysplastic syndrome and secondary acute myeloid leukemia |
title_short | The role of the atypical chemokine receptor CCRL2 in myelodysplastic syndrome and secondary acute myeloid leukemia |
title_sort | role of the atypical chemokine receptor ccrl2 in myelodysplastic syndrome and secondary acute myeloid leukemia |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8856621/ https://www.ncbi.nlm.nih.gov/pubmed/35179961 http://dx.doi.org/10.1126/sciadv.abl8952 |
work_keys_str_mv | AT karantanostheodoros theroleoftheatypicalchemokinereceptorccrl2inmyelodysplasticsyndromeandsecondaryacutemyeloidleukemia AT teodorescupatric theroleoftheatypicalchemokinereceptorccrl2inmyelodysplasticsyndromeandsecondaryacutemyeloidleukemia AT perkinsbrandy theroleoftheatypicalchemokinereceptorccrl2inmyelodysplasticsyndromeandsecondaryacutemyeloidleukemia AT christodoulouilias theroleoftheatypicalchemokinereceptorccrl2inmyelodysplasticsyndromeandsecondaryacutemyeloidleukemia AT estebchristopher theroleoftheatypicalchemokinereceptorccrl2inmyelodysplasticsyndromeandsecondaryacutemyeloidleukemia AT varadhanravi theroleoftheatypicalchemokinereceptorccrl2inmyelodysplasticsyndromeandsecondaryacutemyeloidleukemia AT helmenstineeric theroleoftheatypicalchemokinereceptorccrl2inmyelodysplasticsyndromeandsecondaryacutemyeloidleukemia AT rajkhowatrivikram theroleoftheatypicalchemokinereceptorccrl2inmyelodysplasticsyndromeandsecondaryacutemyeloidleukemia AT paunbogdanc theroleoftheatypicalchemokinereceptorccrl2inmyelodysplasticsyndromeandsecondaryacutemyeloidleukemia AT bonifantchallice theroleoftheatypicalchemokinereceptorccrl2inmyelodysplasticsyndromeandsecondaryacutemyeloidleukemia AT daltonwbrian theroleoftheatypicalchemokinereceptorccrl2inmyelodysplasticsyndromeandsecondaryacutemyeloidleukemia AT gondeklukaszp theroleoftheatypicalchemokinereceptorccrl2inmyelodysplasticsyndromeandsecondaryacutemyeloidleukemia AT moliternoalisonr theroleoftheatypicalchemokinereceptorccrl2inmyelodysplasticsyndromeandsecondaryacutemyeloidleukemia AT levismarkj theroleoftheatypicalchemokinereceptorccrl2inmyelodysplasticsyndromeandsecondaryacutemyeloidleukemia AT ghiaurgabriel theroleoftheatypicalchemokinereceptorccrl2inmyelodysplasticsyndromeandsecondaryacutemyeloidleukemia AT jonesrichardj theroleoftheatypicalchemokinereceptorccrl2inmyelodysplasticsyndromeandsecondaryacutemyeloidleukemia AT karantanostheodoros roleoftheatypicalchemokinereceptorccrl2inmyelodysplasticsyndromeandsecondaryacutemyeloidleukemia AT teodorescupatric roleoftheatypicalchemokinereceptorccrl2inmyelodysplasticsyndromeandsecondaryacutemyeloidleukemia AT perkinsbrandy roleoftheatypicalchemokinereceptorccrl2inmyelodysplasticsyndromeandsecondaryacutemyeloidleukemia AT christodoulouilias roleoftheatypicalchemokinereceptorccrl2inmyelodysplasticsyndromeandsecondaryacutemyeloidleukemia AT estebchristopher roleoftheatypicalchemokinereceptorccrl2inmyelodysplasticsyndromeandsecondaryacutemyeloidleukemia AT varadhanravi roleoftheatypicalchemokinereceptorccrl2inmyelodysplasticsyndromeandsecondaryacutemyeloidleukemia AT helmenstineeric roleoftheatypicalchemokinereceptorccrl2inmyelodysplasticsyndromeandsecondaryacutemyeloidleukemia AT rajkhowatrivikram roleoftheatypicalchemokinereceptorccrl2inmyelodysplasticsyndromeandsecondaryacutemyeloidleukemia AT paunbogdanc roleoftheatypicalchemokinereceptorccrl2inmyelodysplasticsyndromeandsecondaryacutemyeloidleukemia AT bonifantchallice roleoftheatypicalchemokinereceptorccrl2inmyelodysplasticsyndromeandsecondaryacutemyeloidleukemia AT daltonwbrian roleoftheatypicalchemokinereceptorccrl2inmyelodysplasticsyndromeandsecondaryacutemyeloidleukemia AT gondeklukaszp roleoftheatypicalchemokinereceptorccrl2inmyelodysplasticsyndromeandsecondaryacutemyeloidleukemia AT moliternoalisonr roleoftheatypicalchemokinereceptorccrl2inmyelodysplasticsyndromeandsecondaryacutemyeloidleukemia AT levismarkj roleoftheatypicalchemokinereceptorccrl2inmyelodysplasticsyndromeandsecondaryacutemyeloidleukemia AT ghiaurgabriel roleoftheatypicalchemokinereceptorccrl2inmyelodysplasticsyndromeandsecondaryacutemyeloidleukemia AT jonesrichardj roleoftheatypicalchemokinereceptorccrl2inmyelodysplasticsyndromeandsecondaryacutemyeloidleukemia |