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Obesity-induced galectin-9 is a therapeutic target in B-cell acute lymphoblastic leukemia

The incidence of obesity is rising with greater than 40% of the world’s population expected to be overweight or suffering from obesity by 2030. This is alarming because obesity increases mortality rates in patients with various cancer subtypes including leukemia. The survival differences between lea...

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Autores principales: Lee, Miyoung, Hamilton, Jamie A. G., Talekar, Ganesh R., Ross, Anthony J., Michael, Langston, Rupji, Manali, Dwivedi, Bhakti, Raikar, Sunil S., Boss, Jeremy, Scharer, Christopher D., Graham, Douglas K., DeRyckere, Deborah, Porter, Christopher C., Henry, Curtis J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8894417/
https://www.ncbi.nlm.nih.gov/pubmed/35241678
http://dx.doi.org/10.1038/s41467-022-28839-y
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author Lee, Miyoung
Hamilton, Jamie A. G.
Talekar, Ganesh R.
Ross, Anthony J.
Michael, Langston
Rupji, Manali
Dwivedi, Bhakti
Raikar, Sunil S.
Boss, Jeremy
Scharer, Christopher D.
Graham, Douglas K.
DeRyckere, Deborah
Porter, Christopher C.
Henry, Curtis J.
author_facet Lee, Miyoung
Hamilton, Jamie A. G.
Talekar, Ganesh R.
Ross, Anthony J.
Michael, Langston
Rupji, Manali
Dwivedi, Bhakti
Raikar, Sunil S.
Boss, Jeremy
Scharer, Christopher D.
Graham, Douglas K.
DeRyckere, Deborah
Porter, Christopher C.
Henry, Curtis J.
author_sort Lee, Miyoung
collection PubMed
description The incidence of obesity is rising with greater than 40% of the world’s population expected to be overweight or suffering from obesity by 2030. This is alarming because obesity increases mortality rates in patients with various cancer subtypes including leukemia. The survival differences between lean patients and patients with obesity are largely attributed to altered drug pharmacokinetics in patients receiving chemotherapy; whereas, the direct impact of an adipocyte-enriched microenvironment on cancer cells is rarely considered. Here we show that the adipocyte secretome upregulates the surface expression of Galectin-9 (GAL-9) on human B-acute lymphoblastic leukemia cells (B-ALL) which promotes chemoresistance. Antibody-mediated targeting of GAL-9 on B-ALL cells induces DNA damage, alters cell cycle progression, and promotes apoptosis in vitro and significantly extends the survival of obese but not lean mice with aggressive B-ALL. Our studies reveal that adipocyte-mediated upregulation of GAL-9 on B-ALL cells can be targeted with antibody-based therapies to overcome obesity-induced chemoresistance.
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spelling pubmed-88944172022-03-17 Obesity-induced galectin-9 is a therapeutic target in B-cell acute lymphoblastic leukemia Lee, Miyoung Hamilton, Jamie A. G. Talekar, Ganesh R. Ross, Anthony J. Michael, Langston Rupji, Manali Dwivedi, Bhakti Raikar, Sunil S. Boss, Jeremy Scharer, Christopher D. Graham, Douglas K. DeRyckere, Deborah Porter, Christopher C. Henry, Curtis J. Nat Commun Article The incidence of obesity is rising with greater than 40% of the world’s population expected to be overweight or suffering from obesity by 2030. This is alarming because obesity increases mortality rates in patients with various cancer subtypes including leukemia. The survival differences between lean patients and patients with obesity are largely attributed to altered drug pharmacokinetics in patients receiving chemotherapy; whereas, the direct impact of an adipocyte-enriched microenvironment on cancer cells is rarely considered. Here we show that the adipocyte secretome upregulates the surface expression of Galectin-9 (GAL-9) on human B-acute lymphoblastic leukemia cells (B-ALL) which promotes chemoresistance. Antibody-mediated targeting of GAL-9 on B-ALL cells induces DNA damage, alters cell cycle progression, and promotes apoptosis in vitro and significantly extends the survival of obese but not lean mice with aggressive B-ALL. Our studies reveal that adipocyte-mediated upregulation of GAL-9 on B-ALL cells can be targeted with antibody-based therapies to overcome obesity-induced chemoresistance. Nature Publishing Group UK 2022-03-03 /pmc/articles/PMC8894417/ /pubmed/35241678 http://dx.doi.org/10.1038/s41467-022-28839-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Lee, Miyoung
Hamilton, Jamie A. G.
Talekar, Ganesh R.
Ross, Anthony J.
Michael, Langston
Rupji, Manali
Dwivedi, Bhakti
Raikar, Sunil S.
Boss, Jeremy
Scharer, Christopher D.
Graham, Douglas K.
DeRyckere, Deborah
Porter, Christopher C.
Henry, Curtis J.
Obesity-induced galectin-9 is a therapeutic target in B-cell acute lymphoblastic leukemia
title Obesity-induced galectin-9 is a therapeutic target in B-cell acute lymphoblastic leukemia
title_full Obesity-induced galectin-9 is a therapeutic target in B-cell acute lymphoblastic leukemia
title_fullStr Obesity-induced galectin-9 is a therapeutic target in B-cell acute lymphoblastic leukemia
title_full_unstemmed Obesity-induced galectin-9 is a therapeutic target in B-cell acute lymphoblastic leukemia
title_short Obesity-induced galectin-9 is a therapeutic target in B-cell acute lymphoblastic leukemia
title_sort obesity-induced galectin-9 is a therapeutic target in b-cell acute lymphoblastic leukemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8894417/
https://www.ncbi.nlm.nih.gov/pubmed/35241678
http://dx.doi.org/10.1038/s41467-022-28839-y
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