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ResearchIn-Press PreviewInflammationOncology Open Access | 10.1172/JCI188888

T-cell acute lymphoblastic leukemia exploits a neural proinflammatory pathway to colonize the meninges

Nitesh D. Sharma,1 Esra'a Keewan,2 Wojciech Ornatowski,1 Silpita Paul,1 Monique Nysus,2 Christopher C. Barnett,3 Julie Wolfson,3 Quiteria Jacquez,4 Bianca L. Myers,5 Huining Kang,6 Katherine E. Zychowski,4 Stuart S. Winter,7 Mignon L. Loh,8 Stephen P. Hunger,9 Eliseo F. Castillo,10 Tom Taghon,11 Christina Halsey,12 Tou Yia Vue,5 Nicholas Jones,13 Panagiotis Ntziachristos,11 and Ksenia Matlawska-Wasowska1

1Department of Cell Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

2Department of Pediatrics, University of New Mexico, Albuquerque, United States of America

3Department of Pediatrics, University of Alabama at Birmingham, Birmingham, United States of America

4College of Nursing, University of New Mexico, Albuquerque, United States of America

5Department of Neurosciences, University of New Mexico, Albuquerque, United States of America

6Department of Internal Medicine, University of New Mexico, Albuquerque, United States of America

7Children's Minnesota, Minneapolis, United States of America

8Seattle Children's Research Institute and the Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, United States of America

9Department of Pediatrics and the Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, United States of America

10Department of Internal Medicine, Division of Gastroenterology and Hepatolog, University of New Mexico, Albuquerque, United States of America

11Cancer Research Institute Ghent, Ghent, Belgium

12Wolfson Wohl Cancer Research Centre, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

13Institute of Life Science, Swansea University Medical School, Swansea, United Kingdom

Find articles by Sharma, N. in: PubMed | Google Scholar

1Department of Cell Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

2Department of Pediatrics, University of New Mexico, Albuquerque, United States of America

3Department of Pediatrics, University of Alabama at Birmingham, Birmingham, United States of America

4College of Nursing, University of New Mexico, Albuquerque, United States of America

5Department of Neurosciences, University of New Mexico, Albuquerque, United States of America

6Department of Internal Medicine, University of New Mexico, Albuquerque, United States of America

7Children's Minnesota, Minneapolis, United States of America

8Seattle Children's Research Institute and the Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, United States of America

9Department of Pediatrics and the Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, United States of America

10Department of Internal Medicine, Division of Gastroenterology and Hepatolog, University of New Mexico, Albuquerque, United States of America

11Cancer Research Institute Ghent, Ghent, Belgium

12Wolfson Wohl Cancer Research Centre, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

13Institute of Life Science, Swansea University Medical School, Swansea, United Kingdom

Find articles by Keewan, E. in: PubMed | Google Scholar

1Department of Cell Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

2Department of Pediatrics, University of New Mexico, Albuquerque, United States of America

3Department of Pediatrics, University of Alabama at Birmingham, Birmingham, United States of America

4College of Nursing, University of New Mexico, Albuquerque, United States of America

5Department of Neurosciences, University of New Mexico, Albuquerque, United States of America

6Department of Internal Medicine, University of New Mexico, Albuquerque, United States of America

7Children's Minnesota, Minneapolis, United States of America

8Seattle Children's Research Institute and the Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, United States of America

9Department of Pediatrics and the Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, United States of America

10Department of Internal Medicine, Division of Gastroenterology and Hepatolog, University of New Mexico, Albuquerque, United States of America

11Cancer Research Institute Ghent, Ghent, Belgium

12Wolfson Wohl Cancer Research Centre, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

13Institute of Life Science, Swansea University Medical School, Swansea, United Kingdom

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1Department of Cell Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

2Department of Pediatrics, University of New Mexico, Albuquerque, United States of America

3Department of Pediatrics, University of Alabama at Birmingham, Birmingham, United States of America

4College of Nursing, University of New Mexico, Albuquerque, United States of America

5Department of Neurosciences, University of New Mexico, Albuquerque, United States of America

6Department of Internal Medicine, University of New Mexico, Albuquerque, United States of America

7Children's Minnesota, Minneapolis, United States of America

8Seattle Children's Research Institute and the Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, United States of America

9Department of Pediatrics and the Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, United States of America

10Department of Internal Medicine, Division of Gastroenterology and Hepatolog, University of New Mexico, Albuquerque, United States of America

11Cancer Research Institute Ghent, Ghent, Belgium

12Wolfson Wohl Cancer Research Centre, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

13Institute of Life Science, Swansea University Medical School, Swansea, United Kingdom

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1Department of Cell Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

2Department of Pediatrics, University of New Mexico, Albuquerque, United States of America

3Department of Pediatrics, University of Alabama at Birmingham, Birmingham, United States of America

4College of Nursing, University of New Mexico, Albuquerque, United States of America

5Department of Neurosciences, University of New Mexico, Albuquerque, United States of America

6Department of Internal Medicine, University of New Mexico, Albuquerque, United States of America

7Children's Minnesota, Minneapolis, United States of America

8Seattle Children's Research Institute and the Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, United States of America

9Department of Pediatrics and the Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, United States of America

10Department of Internal Medicine, Division of Gastroenterology and Hepatolog, University of New Mexico, Albuquerque, United States of America

11Cancer Research Institute Ghent, Ghent, Belgium

12Wolfson Wohl Cancer Research Centre, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

13Institute of Life Science, Swansea University Medical School, Swansea, United Kingdom

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1Department of Cell Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

2Department of Pediatrics, University of New Mexico, Albuquerque, United States of America

3Department of Pediatrics, University of Alabama at Birmingham, Birmingham, United States of America

4College of Nursing, University of New Mexico, Albuquerque, United States of America

5Department of Neurosciences, University of New Mexico, Albuquerque, United States of America

6Department of Internal Medicine, University of New Mexico, Albuquerque, United States of America

7Children's Minnesota, Minneapolis, United States of America

8Seattle Children's Research Institute and the Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, United States of America

9Department of Pediatrics and the Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, United States of America

10Department of Internal Medicine, Division of Gastroenterology and Hepatolog, University of New Mexico, Albuquerque, United States of America

11Cancer Research Institute Ghent, Ghent, Belgium

12Wolfson Wohl Cancer Research Centre, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

13Institute of Life Science, Swansea University Medical School, Swansea, United Kingdom

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1Department of Cell Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

2Department of Pediatrics, University of New Mexico, Albuquerque, United States of America

3Department of Pediatrics, University of Alabama at Birmingham, Birmingham, United States of America

4College of Nursing, University of New Mexico, Albuquerque, United States of America

5Department of Neurosciences, University of New Mexico, Albuquerque, United States of America

6Department of Internal Medicine, University of New Mexico, Albuquerque, United States of America

7Children's Minnesota, Minneapolis, United States of America

8Seattle Children's Research Institute and the Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, United States of America

9Department of Pediatrics and the Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, United States of America

10Department of Internal Medicine, Division of Gastroenterology and Hepatolog, University of New Mexico, Albuquerque, United States of America

11Cancer Research Institute Ghent, Ghent, Belgium

12Wolfson Wohl Cancer Research Centre, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

13Institute of Life Science, Swansea University Medical School, Swansea, United Kingdom

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1Department of Cell Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

2Department of Pediatrics, University of New Mexico, Albuquerque, United States of America

3Department of Pediatrics, University of Alabama at Birmingham, Birmingham, United States of America

4College of Nursing, University of New Mexico, Albuquerque, United States of America

5Department of Neurosciences, University of New Mexico, Albuquerque, United States of America

6Department of Internal Medicine, University of New Mexico, Albuquerque, United States of America

7Children's Minnesota, Minneapolis, United States of America

8Seattle Children's Research Institute and the Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, United States of America

9Department of Pediatrics and the Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, United States of America

10Department of Internal Medicine, Division of Gastroenterology and Hepatolog, University of New Mexico, Albuquerque, United States of America

11Cancer Research Institute Ghent, Ghent, Belgium

12Wolfson Wohl Cancer Research Centre, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

13Institute of Life Science, Swansea University Medical School, Swansea, United Kingdom

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1Department of Cell Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

2Department of Pediatrics, University of New Mexico, Albuquerque, United States of America

3Department of Pediatrics, University of Alabama at Birmingham, Birmingham, United States of America

4College of Nursing, University of New Mexico, Albuquerque, United States of America

5Department of Neurosciences, University of New Mexico, Albuquerque, United States of America

6Department of Internal Medicine, University of New Mexico, Albuquerque, United States of America

7Children's Minnesota, Minneapolis, United States of America

8Seattle Children's Research Institute and the Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, United States of America

9Department of Pediatrics and the Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, United States of America

10Department of Internal Medicine, Division of Gastroenterology and Hepatolog, University of New Mexico, Albuquerque, United States of America

11Cancer Research Institute Ghent, Ghent, Belgium

12Wolfson Wohl Cancer Research Centre, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

13Institute of Life Science, Swansea University Medical School, Swansea, United Kingdom

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1Department of Cell Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

2Department of Pediatrics, University of New Mexico, Albuquerque, United States of America

3Department of Pediatrics, University of Alabama at Birmingham, Birmingham, United States of America

4College of Nursing, University of New Mexico, Albuquerque, United States of America

5Department of Neurosciences, University of New Mexico, Albuquerque, United States of America

6Department of Internal Medicine, University of New Mexico, Albuquerque, United States of America

7Children's Minnesota, Minneapolis, United States of America

8Seattle Children's Research Institute and the Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, United States of America

9Department of Pediatrics and the Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, United States of America

10Department of Internal Medicine, Division of Gastroenterology and Hepatolog, University of New Mexico, Albuquerque, United States of America

11Cancer Research Institute Ghent, Ghent, Belgium

12Wolfson Wohl Cancer Research Centre, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

13Institute of Life Science, Swansea University Medical School, Swansea, United Kingdom

Find articles by Kang, H. in: PubMed | Google Scholar |

1Department of Cell Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

2Department of Pediatrics, University of New Mexico, Albuquerque, United States of America

3Department of Pediatrics, University of Alabama at Birmingham, Birmingham, United States of America

4College of Nursing, University of New Mexico, Albuquerque, United States of America

5Department of Neurosciences, University of New Mexico, Albuquerque, United States of America

6Department of Internal Medicine, University of New Mexico, Albuquerque, United States of America

7Children's Minnesota, Minneapolis, United States of America

8Seattle Children's Research Institute and the Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, United States of America

9Department of Pediatrics and the Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, United States of America

10Department of Internal Medicine, Division of Gastroenterology and Hepatolog, University of New Mexico, Albuquerque, United States of America

11Cancer Research Institute Ghent, Ghent, Belgium

12Wolfson Wohl Cancer Research Centre, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

13Institute of Life Science, Swansea University Medical School, Swansea, United Kingdom

Find articles by Zychowski, K. in: PubMed | Google Scholar

1Department of Cell Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

2Department of Pediatrics, University of New Mexico, Albuquerque, United States of America

3Department of Pediatrics, University of Alabama at Birmingham, Birmingham, United States of America

4College of Nursing, University of New Mexico, Albuquerque, United States of America

5Department of Neurosciences, University of New Mexico, Albuquerque, United States of America

6Department of Internal Medicine, University of New Mexico, Albuquerque, United States of America

7Children's Minnesota, Minneapolis, United States of America

8Seattle Children's Research Institute and the Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, United States of America

9Department of Pediatrics and the Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, United States of America

10Department of Internal Medicine, Division of Gastroenterology and Hepatolog, University of New Mexico, Albuquerque, United States of America

11Cancer Research Institute Ghent, Ghent, Belgium

12Wolfson Wohl Cancer Research Centre, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

13Institute of Life Science, Swansea University Medical School, Swansea, United Kingdom

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1Department of Cell Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

2Department of Pediatrics, University of New Mexico, Albuquerque, United States of America

3Department of Pediatrics, University of Alabama at Birmingham, Birmingham, United States of America

4College of Nursing, University of New Mexico, Albuquerque, United States of America

5Department of Neurosciences, University of New Mexico, Albuquerque, United States of America

6Department of Internal Medicine, University of New Mexico, Albuquerque, United States of America

7Children's Minnesota, Minneapolis, United States of America

8Seattle Children's Research Institute and the Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, United States of America

9Department of Pediatrics and the Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, United States of America

10Department of Internal Medicine, Division of Gastroenterology and Hepatolog, University of New Mexico, Albuquerque, United States of America

11Cancer Research Institute Ghent, Ghent, Belgium

12Wolfson Wohl Cancer Research Centre, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

13Institute of Life Science, Swansea University Medical School, Swansea, United Kingdom

Find articles by Loh, M. in: PubMed | Google Scholar

1Department of Cell Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

2Department of Pediatrics, University of New Mexico, Albuquerque, United States of America

3Department of Pediatrics, University of Alabama at Birmingham, Birmingham, United States of America

4College of Nursing, University of New Mexico, Albuquerque, United States of America

5Department of Neurosciences, University of New Mexico, Albuquerque, United States of America

6Department of Internal Medicine, University of New Mexico, Albuquerque, United States of America

7Children's Minnesota, Minneapolis, United States of America

8Seattle Children's Research Institute and the Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, United States of America

9Department of Pediatrics and the Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, United States of America

10Department of Internal Medicine, Division of Gastroenterology and Hepatolog, University of New Mexico, Albuquerque, United States of America

11Cancer Research Institute Ghent, Ghent, Belgium

12Wolfson Wohl Cancer Research Centre, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

13Institute of Life Science, Swansea University Medical School, Swansea, United Kingdom

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1Department of Cell Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

2Department of Pediatrics, University of New Mexico, Albuquerque, United States of America

3Department of Pediatrics, University of Alabama at Birmingham, Birmingham, United States of America

4College of Nursing, University of New Mexico, Albuquerque, United States of America

5Department of Neurosciences, University of New Mexico, Albuquerque, United States of America

6Department of Internal Medicine, University of New Mexico, Albuquerque, United States of America

7Children's Minnesota, Minneapolis, United States of America

8Seattle Children's Research Institute and the Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, United States of America

9Department of Pediatrics and the Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, United States of America

10Department of Internal Medicine, Division of Gastroenterology and Hepatolog, University of New Mexico, Albuquerque, United States of America

11Cancer Research Institute Ghent, Ghent, Belgium

12Wolfson Wohl Cancer Research Centre, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

13Institute of Life Science, Swansea University Medical School, Swansea, United Kingdom

Find articles by Castillo, E. in: PubMed | Google Scholar |

1Department of Cell Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

2Department of Pediatrics, University of New Mexico, Albuquerque, United States of America

3Department of Pediatrics, University of Alabama at Birmingham, Birmingham, United States of America

4College of Nursing, University of New Mexico, Albuquerque, United States of America

5Department of Neurosciences, University of New Mexico, Albuquerque, United States of America

6Department of Internal Medicine, University of New Mexico, Albuquerque, United States of America

7Children's Minnesota, Minneapolis, United States of America

8Seattle Children's Research Institute and the Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, United States of America

9Department of Pediatrics and the Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, United States of America

10Department of Internal Medicine, Division of Gastroenterology and Hepatolog, University of New Mexico, Albuquerque, United States of America

11Cancer Research Institute Ghent, Ghent, Belgium

12Wolfson Wohl Cancer Research Centre, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

13Institute of Life Science, Swansea University Medical School, Swansea, United Kingdom

Find articles by Taghon, T. in: PubMed | Google Scholar

1Department of Cell Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

2Department of Pediatrics, University of New Mexico, Albuquerque, United States of America

3Department of Pediatrics, University of Alabama at Birmingham, Birmingham, United States of America

4College of Nursing, University of New Mexico, Albuquerque, United States of America

5Department of Neurosciences, University of New Mexico, Albuquerque, United States of America

6Department of Internal Medicine, University of New Mexico, Albuquerque, United States of America

7Children's Minnesota, Minneapolis, United States of America

8Seattle Children's Research Institute and the Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, United States of America

9Department of Pediatrics and the Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, United States of America

10Department of Internal Medicine, Division of Gastroenterology and Hepatolog, University of New Mexico, Albuquerque, United States of America

11Cancer Research Institute Ghent, Ghent, Belgium

12Wolfson Wohl Cancer Research Centre, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

13Institute of Life Science, Swansea University Medical School, Swansea, United Kingdom

Find articles by Halsey, C. in: PubMed | Google Scholar

1Department of Cell Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

2Department of Pediatrics, University of New Mexico, Albuquerque, United States of America

3Department of Pediatrics, University of Alabama at Birmingham, Birmingham, United States of America

4College of Nursing, University of New Mexico, Albuquerque, United States of America

5Department of Neurosciences, University of New Mexico, Albuquerque, United States of America

6Department of Internal Medicine, University of New Mexico, Albuquerque, United States of America

7Children's Minnesota, Minneapolis, United States of America

8Seattle Children's Research Institute and the Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, United States of America

9Department of Pediatrics and the Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, United States of America

10Department of Internal Medicine, Division of Gastroenterology and Hepatolog, University of New Mexico, Albuquerque, United States of America

11Cancer Research Institute Ghent, Ghent, Belgium

12Wolfson Wohl Cancer Research Centre, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

13Institute of Life Science, Swansea University Medical School, Swansea, United Kingdom

Find articles by Vue, T. in: PubMed | Google Scholar

1Department of Cell Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

2Department of Pediatrics, University of New Mexico, Albuquerque, United States of America

3Department of Pediatrics, University of Alabama at Birmingham, Birmingham, United States of America

4College of Nursing, University of New Mexico, Albuquerque, United States of America

5Department of Neurosciences, University of New Mexico, Albuquerque, United States of America

6Department of Internal Medicine, University of New Mexico, Albuquerque, United States of America

7Children's Minnesota, Minneapolis, United States of America

8Seattle Children's Research Institute and the Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, United States of America

9Department of Pediatrics and the Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, United States of America

10Department of Internal Medicine, Division of Gastroenterology and Hepatolog, University of New Mexico, Albuquerque, United States of America

11Cancer Research Institute Ghent, Ghent, Belgium

12Wolfson Wohl Cancer Research Centre, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

13Institute of Life Science, Swansea University Medical School, Swansea, United Kingdom

Find articles by Jones, N. in: PubMed | Google Scholar |

1Department of Cell Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

2Department of Pediatrics, University of New Mexico, Albuquerque, United States of America

3Department of Pediatrics, University of Alabama at Birmingham, Birmingham, United States of America

4College of Nursing, University of New Mexico, Albuquerque, United States of America

5Department of Neurosciences, University of New Mexico, Albuquerque, United States of America

6Department of Internal Medicine, University of New Mexico, Albuquerque, United States of America

7Children's Minnesota, Minneapolis, United States of America

8Seattle Children's Research Institute and the Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, United States of America

9Department of Pediatrics and the Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, United States of America

10Department of Internal Medicine, Division of Gastroenterology and Hepatolog, University of New Mexico, Albuquerque, United States of America

11Cancer Research Institute Ghent, Ghent, Belgium

12Wolfson Wohl Cancer Research Centre, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

13Institute of Life Science, Swansea University Medical School, Swansea, United Kingdom

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1Department of Cell Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

2Department of Pediatrics, University of New Mexico, Albuquerque, United States of America

3Department of Pediatrics, University of Alabama at Birmingham, Birmingham, United States of America

4College of Nursing, University of New Mexico, Albuquerque, United States of America

5Department of Neurosciences, University of New Mexico, Albuquerque, United States of America

6Department of Internal Medicine, University of New Mexico, Albuquerque, United States of America

7Children's Minnesota, Minneapolis, United States of America

8Seattle Children's Research Institute and the Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, United States of America

9Department of Pediatrics and the Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, United States of America

10Department of Internal Medicine, Division of Gastroenterology and Hepatolog, University of New Mexico, Albuquerque, United States of America

11Cancer Research Institute Ghent, Ghent, Belgium

12Wolfson Wohl Cancer Research Centre, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

13Institute of Life Science, Swansea University Medical School, Swansea, United Kingdom

Find articles by Matlawska-Wasowska, K. in: PubMed | Google Scholar

Published October 23, 2025 - More info

J Clin Invest. https://doi.org/10.1172/JCI188888.
Copyright © 2025, Sharma et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published October 23, 2025 - Version history
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Abstract

Infiltration of T-cell acute lymphoblastic leukemia (T-ALL) into the meninges worsens prognosis, underscoring the need to understand mechanisms driving meningeal involvement. Here, we show that T-ALL cells expressing CXCR3 exploit normal T-cell function to infiltrate the inflamed meninges. CXCR3 deletion hampered disease progression and extramedullary dissemination by reducing leukemic cell proliferation and migration. Conversely, forced expression of CXCR3 facilitated T-ALL trafficking to the meninges. We identified the ubiquitin-specific protease 7 as a key regulator of CXCR3 protein stability in T-ALL. Furthermore, we discovered elevated levels of CXCL10, a CXCR3 ligand, in the cerebrospinal fluid from T-ALL patients and leukemia-bearing mice. Our studies demonstrate that meningeal stromal cells, specifically pericytes and fibroblasts, induce CXCL10 expression in response to leukemia, and that loss of CXCL10 attenuated T-ALL influx into the meninges. Moreover, we report that leukemia-derived proinflammatory cytokines, TNFα, IL27 and IFNγ, induced CXCL10 in the meningeal stroma. Pharmacological inhibition or deletion of CXCR3 or CXCL10 reduced T-ALL cell migration and adhesion to meningeal stromal cells. Finally, we reveal that CXCR3 and CXCL10 upregulated VLA-4/VCAM-1 signaling, promoting cell-cell adhesion and thus T-ALL retention in the meninges. Our findings highlight the pivotal role of CXCR3-CXCL10 signaling in T-ALL progression and meningeal colonization.

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graphical abstract
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