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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...

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Autores principales: 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.
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
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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.
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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
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