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

Silvia Buonamici, Thomas Trimarchi, Maria Grazia Ruocco, Linsey Reavie, Severine Cathelin, Brenton G. Mar, Apostolos Klinakis, Yevgeniy Lukyanov, Jen-Chieh Tseng, Filiz Sen, Eric Gehrie, Mengling Li, Elizabeth Newcomb, Jiri Zavadil, Daniel Meruelo, Martin Lipp, Sherif Ibrahim, Argiris Efstratiadis, David Zagzag, Jonathan S. Bromberg, Michael L. Dustin and Iannis Aifantis ()
Additional contact information
Silvia Buonamici: Department of Pathology and New York University Cancer Institute,
Thomas Trimarchi: Department of Pathology and New York University Cancer Institute,
Maria Grazia Ruocco: Department of Pathology and New York University Cancer Institute,
Linsey Reavie: Department of Pathology and New York University Cancer Institute,
Severine Cathelin: Department of Pathology and New York University Cancer Institute,
Brenton G. Mar: Department of Pediatrics,
Apostolos Klinakis: Columbia University Medical Center, New York, New York 10032, USA
Yevgeniy Lukyanov: Department of Pathology and New York University Cancer Institute,
Jen-Chieh Tseng: Department of Pathology and New York University Cancer Institute,
Filiz Sen: Department of Pathology and New York University Cancer Institute,
Eric Gehrie: and the Immunology Institute, Mount Sinai School of Medicine, New York, New York 10029, USA
Mengling Li: New York University Cancer Institute, New York, New York 10016, USA
Elizabeth Newcomb: Department of Pathology and New York University Cancer Institute,
Jiri Zavadil: Department of Pathology and New York University Cancer Institute,
Daniel Meruelo: Department of Pathology and New York University Cancer Institute,
Martin Lipp: Max-Delbrück-Center for Molecular Medicine
Sherif Ibrahim: Department of Pathology and New York University Cancer Institute,
Argiris Efstratiadis: Columbia University Medical Center, New York, New York 10032, USA
David Zagzag: Department of Pathology and New York University Cancer Institute,
Jonathan S. Bromberg: and the Immunology Institute, Mount Sinai School of Medicine, New York, New York 10029, USA
Michael L. Dustin: Department of Pathology and New York University Cancer Institute,
Iannis Aifantis: Department of Pathology and New York University Cancer Institute,

Nature, 2009, vol. 459, issue 7249, 1000-1004

Abstract: CNS infiltration in leukaemia T-cell acute leukaemias (T-ALL) often show central nervous system (CNS) infiltration that has to be treated aggressively. In most T-ALL cases, the Notch signalling pathway is constitutionally activated. Buonamici et al. now show that Notch signalling induces the expression of the cytokine receptor CCR7. CCR7 is shown to be responsible for the trafficking of T-ALL cells to the CNS; this appears to involve the expression of the CCR7 ligand CCL19 on brain endothelial cells. Targeting CCR7 may thus offer a therapeutic approach to prevent CNS relapse in T-ALL patients.

Date: 2009
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DOI: 10.1038/nature08020

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