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Cited by 263

The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.

CCR7 signalling as an essential regulator of CNS infiltration in T-cell leukaemia

Open access
Buonamici, Silvia, Trimarchi, Thomas, Ruocco, Maria Grazia, Reavie, Linsey, Cathelin, Severine, Mar, Brenton G., Klinakis, Apostolos, Lukyanov, Yevgeniy, Tseng, Jen-Chieh, Sen, Filiz, Gehrie, Eric, Li, Mengling, Newcomb, Elizabeth, Zavadil, Jiri, Meruelo, Daniel, Lipp, Martin, Ibrahim, Sherif, Efstratiadis, Argiris, Zagzag, David, Bromberg, Jonathan S., Dustin, Michael L., Aifantis, Iannis·2009·Nature
DOI 10.1038/nature08020
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Abstract

T-cell acute lymphoblastic leukaemia (T-ALL) is a blood malignancy afflicting mainly children and adolescents. T-ALL patients present at diagnosis with increased white cell counts and hepatosplenomegaly, and are at an increased risk of central nervous system (CNS) relapse. For that reason, T-ALL patients usually receive cranial irradiation in addition to intensified intrathecal chemotherapy. The marked increase in survival is thought to be worth the considerable side-effects associated with this therapy. Such complications include secondary tumours, neurocognitive deficits, endocrine disorders and growth impairment. Little is known about the mechanism of leukaemic cell infiltration of the CNS, despite its clinical importance. Here we show, using T-ALL animal modelling and gene-expression profiling, that the chemokine receptor CCR7 (ref. 5) is the essential adhesion signal required for the targeting of leukaemic T-cells into the CNS. Ccr7 gene expression is controlled by the activity of the T-ALL oncogene Notch1 and is expressed in human tumours carrying Notch1-activating mutations. Silencing of either CCR7 or its chemokine ligand CCL19 (ref. 6) in an animal model of T-ALL specifically inhibits CNS infiltration. Furthermore, murine CNS-targeting by human T-ALL cells depends on their ability to express CCR7. These studies identify a single chemokine–receptor interaction as a CNS ‘entry’ signal, and open the way for future pharmacological targeting. Targeted inhibition of CNS involvement in T-ALL could potentially decrease the intensity of CNS-targeted therapy, thus reducing its associated short- and long-term complications.

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Metadata

Authors
Buonamici, S., Trimarchi, T., Ruocco, M. G., Reavie, L., Cathelin, S., Mar, B. G., Klinakis, A., Lukyanov, Y., Tseng, J.-C., Sen, F., Gehrie, E., Li, M., Newcomb, E., Zavadil, J., Meruelo, D., Lipp, M., Ibrahim, S., Efstratiadis, A., Zagzag, D., Bromberg, J. S., Dustin, M. L., & Aifantis, I.
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2009-06
Volume
459
Issue
7249
Pages
1000-1004
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature08020
OpenAlex
W2086943873
Cited by
263
References
28
FWCI
22.23
Type
journal article
Language
en
Open access
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CoChat. (2026). Citation check: CCR7 signalling as an essential regulator of CNS infiltration in T-cell leukaemia. https://app.cochat.ai/papers/10.1038/nature08020
The paper
Buonamici, S., Trimarchi, T., Ruocco, M. G., Reavie, L., Cathelin, S., Mar, B. G., Klinakis, A., Lukyanov, Y., Tseng, J.-C., Sen, F., Gehrie, E., Li, M., Newcomb, E., Zavadil, J., Meruelo, D., Lipp, M., Ibrahim, S., Efstratiadis, A., Zagzag, D., . . . Aifantis, I. (2009). CCR7 signalling as an essential regulator of CNS infiltration in T-cell leukaemia. Nature. https://doi.org/10.1038/nature08020

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.