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HS1 has a central role in the trafficking and homing of leukemic B cells.

Scielzo, Cristina, Bertilaccio, Maria T. S., Simonetti, Giorgia, Dagklis, Antonis, ten Hacken, Elisa, Fazi, Claudia, Muzio, Marta, Caiolfa, Valeria, Kitamura, Daisuke, Restuccia, Umberto, Bachi, Angela, Rocchi, Martina, Ponzoni, Maurilio, Ghia, Paolo, Caligaris-Cappio, Federico·2010·Blood

Abstract

The function of the intracellular protein hematopoietic cell–specific Lyn substrate-1 (HS1) in B lymphocytes is poorly defined. To investigate its role in migration, trafficking, and homing of leukemic B lymphocytes we have used B cells from HS1−/− mice, the HS1-silenced human chronic lymphocytic leukemia (CLL) MEC1 cell line and primary leukemic B cells from patients with CLL. We have used both in vitro and in vivo models and found that the lack of expression of HS1 causes several important functional effects. In vitro, we observed an impaired cytoskeletal remodeling that resulted in diminished cell migration, abnormal cell adhesion, and increased homotypic aggregation. In vivo, immunodeficient Rag2−/−γc−/− mice injected with HS1-silenced CLL B cells showed a decreased organ infiltration with the notable exception of the bone marrow (BM). The leukemic-prone Eμ-TCL1 transgenic mice crossed with HS1-deficient mice were compared with Eμ-TCL1 mice and showed an earlier disease onset and a reduced survival. These findings show that HS1 is a central regulator of cytoskeleton remodeling that controls lymphocyte trafficking and homing and significantly influences the tissue invasion and infiltration in CLL.

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Crossref · 10.1182/blood-2009-12-258814

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Research works printed but not linked: 38

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Cited by

Metadata

Authors
Scielzo, C., Bertilaccio, M. T. S., Simonetti, G., Dagklis, A., ten Hacken, E., Fazi, C., Muzio, M., Caiolfa, V., Kitamura, D., Restuccia, U., Bachi, A., Rocchi, M., Ponzoni, M., Ghia, P., & Caligaris-Cappio, F.
Affiliations
  • Unit of Lymphoid Malignancies, Division of Molecular Oncology, San Raffaele Scientific Institute, Milano, Italy;
  • Unit of B Cell Neoplasia, Division of Molecular Oncology, San Raffaele Scientific Institute, Milano, Italy;
  • Unit of Dynamic Fluorescence Spectroscopy, Division of Molecular Oncology,
  • Division of Molecular Biology, Research Institute for Biological Sciences, Tokyo University of Science, Tokyo, Japan;
  • Università degli Studi di Milano, Milano, Italy;
  • Biomolecular Mass Spectrometry Unit, Division of Genetics and Cell Biology,
  • Pathology Unit, Division of Molecular Oncology, San Raffaele Scientific Institute, Milano, Italy;
Venue
Blood
Published
2010-11-04
Volume
116
Issue
18
Pages
3537-3546
ISSN
  • 0006-4971
  • 1528-0020
Cited by
74
References
0
Language
en

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