IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-28839-y.html
   My bibliography  Save this article

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

Author

Listed:
  • Miyoung Lee

    (Emory University School of Medicine and Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta)

  • Jamie A. G. Hamilton

    (Emory University School of Medicine and Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta)

  • Ganesh R. Talekar

    (Emory University School of Medicine and Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta)

  • Anthony J. Ross

    (Indiana University School of Medicine, Indianapolis)

  • Langston Michael

    (Wake Forest University)

  • Manali Rupji

    (Winship Cancer Institute)

  • Bhakti Dwivedi

    (Winship Cancer Institute)

  • Sunil S. Raikar

    (Emory University School of Medicine and Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta)

  • Jeremy Boss

    (Emory University School of Medicine)

  • Christopher D. Scharer

    (Emory University School of Medicine)

  • Douglas K. Graham

    (Emory University School of Medicine and Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta)

  • Deborah DeRyckere

    (Emory University School of Medicine and Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta)

  • Christopher C. Porter

    (Emory University School of Medicine and Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta)

  • Curtis J. Henry

    (Emory University School of Medicine and Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta)

Abstract

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.

Suggested Citation

  • Miyoung Lee & Jamie A. G. Hamilton & Ganesh R. Talekar & Anthony J. Ross & Langston Michael & Manali Rupji & Bhakti Dwivedi & Sunil S. Raikar & Jeremy Boss & Christopher D. Scharer & Douglas K. Graham, 2022. "Obesity-induced galectin-9 is a therapeutic target in B-cell acute lymphoblastic leukemia," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28839-y
    DOI: 10.1038/s41467-022-28839-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-28839-y
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-28839-y?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Adela Hruby & Frank Hu, 2015. "The Epidemiology of Obesity: A Big Picture," PharmacoEconomics, Springer, vol. 33(7), pages 673-689, July.
    2. Reut Yosef & Noam Pilpel & Ronit Tokarsky-Amiel & Anat Biran & Yossi Ovadya & Snir Cohen & Ezra Vadai & Liat Dassa & Elisheva Shahar & Reba Condiotti & Ittai Ben-Porath & Valery Krizhanovsky, 2016. "Directed elimination of senescent cells by inhibition of BCL-W and BCL-XL," Nature Communications, Nature, vol. 7(1), pages 1-11, September.
    3. N. Giovannone & J. Liang & A. Antonopoulos & J. Geddes Sweeney & S. L. King & S. M. Pochebit & N. Bhattacharyya & G. S. Lee & A. Dell & H. R. Widlund & S. M. Haslam & C. J. Dimitroff, 2018. "Galectin-9 suppresses B cell receptor signaling and is regulated by I-branching of N-glycans," Nature Communications, Nature, vol. 9(1), pages 1-17, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Cezary Wojtyla & Pawel Stanirowski & Pawel Gutaj & Michal Ciebiera & Andrzej Wojtyla, 2021. "Perinatal Outcomes in a Population of Diabetic and Obese Pregnant Women—The Results of the Polish National Survey," IJERPH, MDPI, vol. 18(2), pages 1-14, January.
    2. Arnulf Josef Hartl & Johanna Freidl & Daniela Huber, 2023. "Effects of Alpine Natural Health Resources on Human Health and Wellbeing," IJERPH, MDPI, vol. 20(12), pages 1-3, June.
    3. Rafael M. Tassitano & Robert G. Weaver & Maria Cecília M. Tenório & Keith Brazendale & Michael W. Beets, 2020. "Clusters of non-dietary obesogenic behaviors among adolescents in Brazil: a latent profile analysis," International Journal of Public Health, Springer;Swiss School of Public Health (SSPH+), vol. 65(6), pages 881-891, July.
    4. Ivan Parise & Penelope Abbott & Steven Trankle, 2021. "Drivers to Obesity—A Study of the Association between Time Spent Commuting Daily and Obesity in the Nepean Blue Mountains Area," IJERPH, MDPI, vol. 19(1), pages 1-14, December.
    5. Sinead O’Mahony & Clare B. O’Donovan & Nuala Collins & Kevin Burke & Gerardine Doyle & Eileen R. Gibney, 2023. "Reformulation of Processed Yogurt and Breakfast Cereals over Time: A Scoping Review," IJERPH, MDPI, vol. 20(4), pages 1-15, February.
    6. Joann Chongsaritsinsuk & Alexandra D. Steigmeyer & Keira E. Mahoney & Mia A. Rosenfeld & Taryn M. Lucas & Courtney M. Smith & Alice Li & Deniz Ince & Fiona L. Kearns & Alexandria S. Battison & Marie A, 2023. "Glycoproteomic landscape and structural dynamics of TIM family immune checkpoints enabled by mucinase SmE," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    7. Silvia Coronado-Ferrer & Antonia Ferrer-Sapena & Rafael Aleixandre-Benavent & Juan Carlos Valderrama Zurián & Lourdes Castelló Cogollos, 2022. "Global Trends in Scientific Research on Pediatric Obesity," IJERPH, MDPI, vol. 19(3), pages 1-15, January.
    8. Jaskaren Kohli & Chen Ge & Eleni Fitsiou & Miriam Doepner & Simone M. Brandenburg & William J. Faller & Todd W. Ridky & Marco Demaria, 2022. "Targeting anti-apoptotic pathways eliminates senescent melanocytes and leads to nevi regression," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    9. Hongli Li & Yuanzhong Xu & Yanyan Jiang & Zhiying Jiang & Joshua Otiz-Guzman & Jessie C. Morrill & Jing Cai & Zhengmei Mao & Yong Xu & Benjamin R. Arenkiel & Cheng Huang & Qingchun Tong, 2023. "The melanocortin action is biased toward protection from weight loss in mice," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    10. Vanessa Smer-Barreto & Andrea Quintanilla & Richard J. R. Elliott & John C. Dawson & Jiugeng Sun & Víctor M. Campa & Álvaro Lorente-Macías & Asier Unciti-Broceta & Neil O. Carragher & Juan Carlos Acos, 2023. "Discovery of senolytics using machine learning," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    11. Matthew A. Cottam & Heather L. Caslin & Nathan C. Winn & Alyssa H. Hasty, 2022. "Multiomics reveals persistence of obesity-associated immune cell phenotypes in adipose tissue during weight loss and weight regain in mice," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    12. Alexander Bentley, R. & Ruck, Damian J. & Fouts, Hillary N., 2020. "U.S. obesity as delayed effect of excess sugar," Economics & Human Biology, Elsevier, vol. 36(C).
    13. Riki Tanaka & Sayuri Fuse-Hamaoka & Miyuki Kuroiwa & Yuko Kurosawa & Tasuki Endo & Ryotaro Kime & Takeshi Yoneshiro & Takafumi Hamaoka, 2022. "The Effects of 10-Week Strength Training in the Winter on Brown-like Adipose Tissue Vascular Density," IJERPH, MDPI, vol. 19(16), pages 1-11, August.
    14. Joreintje D. Mackenbach & Marielle A. Beenackers & J. Mark Noordzij & Joost Oude Groeniger & Jeroen Lakerveld & Frank J. van Lenthe, 2019. "The Moderating Role of Self-Control and Financial Strain in the Relation between Exposure to the Food Environment and Obesity: The GLOBE Study," IJERPH, MDPI, vol. 16(4), pages 1-12, February.
    15. Tom G. Richardson & Daniel J. M. Crouch & Grace M. Power & Fernanda Morales-Berstein & Emma Hazelwood & Si Fang & Yoonsu Cho & Jamie R. J. Inshaw & Catherine C. Robertson & Carlo Sidore & Francesco Cu, 2022. "Childhood body size directly increases type 1 diabetes risk based on a lifecourse Mendelian randomization approach," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    16. Lucija Stetic & Ivan Belcic & Goran Sporis & Leon Stetic & Nikola Starcevic, 2021. "Influence of Physical Activity on the Regulation of Disease of Elderly Persons with Metabolic Syndrome," IJERPH, MDPI, vol. 18(1), pages 1-17, January.
    17. Hadis Dastgerdizad & Rachael D. Dombrowski & Bree Bode & Kathryn A. G. Knoff & Noel Kulik & James Mallare & Ravneet Kaur & Heather Dillaway, 2023. "Community Solutions to Increase the Healthfulness of Grocery Stores: Perspectives of Immigrant Parents," IJERPH, MDPI, vol. 20(15), pages 1-20, August.
    18. Corazza, Ilaria & Pennucci, Francesca & De Rosis, Sabina, 2021. "Promoting healthy eating habits among youth according to their preferences: Indications from a discrete choice experiment in Tuscany," Health Policy, Elsevier, vol. 125(7), pages 947-955.
    19. Theresa Kissel & Veerle F. A. M. Derksen & Arthur E. H. Bentlage & Carolien Koeleman & Lise Hafkenscheid & Diane Woude & Manfred Wuhrer & Gestur Vidarsson & René E. M. Toes, 2024. "N-linked Fc glycosylation is not required for IgG-B-cell receptor function in a GC-derived B-cell line," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    20. Robert A. Saxton & Nathanael A. Caveney & Maria Dolores Moya-Garzon & Karsten D. Householder & Grayson E. Rodriguez & Kylie A. Burdsall & Jonathan Z. Long & K. Christopher Garcia, 2023. "Structural insights into the mechanism of leptin receptor activation," Nature Communications, Nature, vol. 14(1), pages 1-10, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28839-y. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.